Two new coumarin glycosides were isolated and purified from the dichloromethane fraction of Angelica biserrata 75% ethanol extract using silica gel, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography. Through the comprehensive use of modern spectroscopic methods, their structures were identified as angelmanetin A (1) and angelmanetin B (2), respectively.

ObjectiveTo investigate the value of third lumbar skeletal muscle mass index （L3-SMI） in predicting the long-term prognosis of patients with acute-on-chronic liver failure （ACLF）， and to provide a useful tool for prognostic scoring of ACLF patients. MethodsA retrospective analysis was performed for the data of 126 patients who underwent abdominal computed tomography （CT） scanning and were diagnosed with ACLF in Shanxi Bethune Hospital from December 2017 to December 2021， including clinical indicators， biochemical parameters， and model for end-stage liver disease （MELD） score， and L3-SMI was calculated. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic （ROC） curve was used to assess the diagnostic value of L3-SMI and other variables （MELD score and Child-Pugh score）， and the DeLong test was used for comparison of the area under the ROC curve （AUC）. ResultsAmong the 126 patients enrolled， 44 （35%） died within 2 years and 82 （65%） survived. Compared with the survival group， the death group had significantly higher age， incidence rate of ascites， international normalized ratio， MELD score， and Child-Pugh score （all P<0.05） and a significantly lower value of L3-SMI ［38.40 （35.95‍ ‍—‍ ‍46.29） cm²/m² vs 44.19 （40.20‍ ‍—‍ ‍48.58） cm²/m²， Z=-2.855， P=0.004］. L3-SMI had an AUC of 0.720 in predicting 2-year mortality in ACLF patients， with a sensitivity of 63.6% and a specificity of 80.5%， and a combination of L3-SMI， MELD score， and Child-Pugh score had a significantly better AUC than a combination of MELD score and Child-Pugh score in predicting 2-year mortality （0.809 vs 0.757， Z=2.015， P<0.05）. ConclusionL3-SMI has a high predictive value for the prognosis of ACLF patients， and the combination of L3-SMI、MELD score and Child-Pugh score has a higher predictive value for ACLF patients， and the inclusion of L3-SMI or sarcopenia in the conventional prognostic scores of ACLF patients may increase the ability to predict disease progression.

Objective: To explore the effects of whole wheat flour on blood glucose and lipid levels and antioxidant capacity of high-fat fed mice. Methods: Thirty-two male C57BL/6J mice at ages of 3 to 4 weeks were randomly divided into 4 groups with 8 mice in each group. The normal control group was fed with ordinary diet, the high-fat diet group was fed with high-fat diet, the whole wheat flour group was fed with high-fat diet and whole wheat flour, and the refined wheat flour group was fed with high-fat diet and refined wheat flour. Nine weeks later, blood was collected from the tail for measurement of fasting blood glucose (FBG), and blood was also collected from the eyeball to determine the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA). Adipose tissue was taken and weighed after death. Body weight, total food intake, Lee's index, adipose index, blood glucose, blood lipids, and antioxidant indicators were compared among the four groups of mice. Results: Compared with the normal control group, the mice in the high-fat diet group, whole wheat flour group, and refined wheat flour group exhibited increased body weight, total food intake, Lee's index, and adipose index, as well as decreased GSH-Px levels; the high-fat diet group had elevated levels of TC, TG, LDL-C and MDA (all P<0.05). When compared to the high-fat diet group, the whole wheat flour group showed lower Lee's index and adipose index, but the difference was not statistically significant (both P>0.05). Both the whole wheat flour group and the refined wheat flour group had reduced levels of TC, TG, LDL-C, and MDA, as well as increased GSH-Px levels (all P<0.05). Conclusions Whole wheat flour can effectively reduce the body weight of high-fat feeding mice, improve blood lipid levels, and enhance antioxidant capacity. However, there was no significant difference in the effects of whole wheat flour and refined wheat flour on mice during the experimental period.

Objective:To summarize and analyze the clinical outcome of minimally invasive McKeown esophagectomy for esophageal squamous cell carcinoma.Methods:We retrospectively analyzed the clinical data of patients with esophageal squamous cell carcinoma who received minimally invasive McKeown esophagectomy in Peking Union Medical College Hospital from January 2017 to December 2022. Improved anesthesia methods, monitoring of recurrent laryngeal nerve, minimally invasive gastrostomy, and jejunostomy techniques were introduced in surgical procedure. We evaluated perioperative data and long-term follow-up survival in these patients.Results:A total of 226 esophageal squamous cell carcinoma patients who met the inclusion and exclusion criteria were enrolled, of which 48.2% received neoadjuvant therapy. The mean operation time was( 327 ± 68) min, with a total of 40.5(33, 50) lymph nodes and 27(19, 33) thoracic lymph nodes harvested. The postoperative hospital stay was 9(7, 12) days, and the postoperative complication rate was 36.3%. In terms of learning curve, after 50 patients intraoperative blood loss, postoperative hospital stay, and recurrent laryngeal nerve injury rate were significantly decreased. The number of total lymph nodes, thoracic lymph nodes, and the 106tbl harvested was significantly increased. The median follow-up time was 23.5(14, 47) months, with a loss of follow-up rate of 3.5%. The overall 2-year and 5-year survival rates were 82.6% and 71.8%, respectively.Conclusion:Improved minimally invasive McKeown esophagectomy for esophageal squamous cell carcinoma are safe and acceptable. Learning curve can be shortened, with increased lymph node harvested and decreased postoperative complications, which improving the short-term and long-term outcomes of patients.

Pharmaceutical cocrystals is an advanced technology to improve the physicochemical and biological properties of drugs. However, there are few studies on the in vivo metabolism of pharmaceutical cocrystals. In this study, the pharmacokinetics of wogonin cocrystal in normal rats was further studied on the basis of the previous preparation of wogonin-aloperine cocrystal. Firstly, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for simultaneous determination of wogonin and its metabolite wogonoside in rat plasma, and to investigate the methodology. The method was applied to the pharmacokinetic study of wogonin-aloperine cocrystal (Wog-Alop) in rats. The results showed that wogonin and its metabolite wogonoside had a good linear relationship in the range of 1-800 ng·mL^-1, and the precision, accuracy, matrix effect and stability in this range met the requirements of biological analysis. Compared with direct administration of wogonin, the C_max of wogonin and its metabolite in rats increased to 7.44-fold and 9.15-fold, AUC_0-t increased to 1.67-fold and 3.72-fold, and oral bioavailability of wogonin increased to 187.66% after cocrystal administration. Wog-Alop cocrystal can significantly improve the C_max, AUC, and oral bioavailability of wogonin and its metabolite, which provides a new perspective for the clinical application of wogonin. This study was approved by the Experimental Animal Ethics Review Committee of Beijing University of Chinese Medicine (approval number: BUCM-2023032307-1148).

BACKGROUND:The clinical application of Mongolian Medicine Erdun-uril in the treatment of osteoarthritis is effective,but its therapeutic effect and related mechanism are still unclear. OBJECTIVE:To observe the repairing process of osteoarthritis in rats by Mongolian Medicine Erdun-uril and analyze its mechanism. METHODS:Thirty male Sprague-Dawley rats(8 weeks of age)were selected to establsih an osteoarthritis model using intraarticular injection of sodium iodoacetate solution into the unilateral knee joint.Two weeks after modeling,the model rats were randomly divided into three groups:control group(n=6)was given normal saline by gavage,and low and high dose groups(n=12 per group)were given Erdun-uril 1.4 and 2 g,respectively,3 times per day.After 2 and 4 weeks of continuous administration,blood samples,articular cartilage and periarticular bone tissue were taken from rats to detect changes in cartilage metabolic markers(cartilage oligomeric matrix protein,proteoglycan),bone metabolic markers(bone alkaline phosphatase,keratan sulfate),inflammatory markers(interleukin 6,tumor necrosis factor α),lipid metabolic markers(total cholesterol,triacylglycerol).Histopathological changes were also observed. RESULTS AND CONCLUSION:qRT-PCR results showed that after 2 and 4 weeks of administration,the mRNA expression of cartilage oligomeric matrix protein,proteoglycan and bone alkaline phosphatase and keratan sulfate in knee cartilage of rats were significantly reduced in the low and high dose groups compared with the control group(P<0.05,P<0.01,P<0.001),with the reduction being more significant in the high dose group.After 2 and 4 weeks of administration,compared with the control group,serum tumor necrosis factor α and interleukin 6 levels were decreased(P<0.01,P<0.001)and total cholesterol and triacylglycerol levels were increased(P<0.05,P<0.01,P<0.001)in the low and high dose groups,with the improvement being more significant in the high dose group.Hematoxylin-eosin staining results showed that in the control group,there were large defective areas on the surface of the knee cartilage with unknown structure and severe inflammatory cell infiltration;in the low dose group,the surface of the knee cartilage was rough with disordered cell arrangement and the cartilage structure did not improve significantly after 2 weeks of administration,while the number of inflammatory cells in the knee cartilage was reduced and the cartilage structure was restored to some extent after 4 weeks of administration;in the high dose group,the structure of the knee cartilage become clear after 2 weeks of administration and even clearer after 4 weeks of administration,and the inflammation was significantly reduced after 2 weeks of administration.To conclude,Mongolian Medicine Erdun-uril with better anti-inflammatory properties can improve cartilage metabolism and obviously alleviate osteoarthritis in rats.

Objective To explore the expression level of miR-34a-5p in pancreatic cancer cell PANC-1 and its effect on epithelial mesenchymal transition(EMT),cell invasion,metastasis,and chemotherapy resistance.Methods Construct stable transfected PANC-1/miR-34a-5p cells or PANC-1/mock cells,and divide the cells into four groups:PANC-1 group,PANC-1/miR-34a-5p group,PANC-1/mock group and PANC-1/miR-34a-5p+gemcitabine group.All four groups of cells were cultured for 24 h.Real-time quantitative polymerase chain reaction was used to detect the expression of miR-34a-5p in PANC-1 cells before and after transfection;Western blotting was used to detect the expression of EMT-related proteins;wound healing experiment was used to detect cell migration ability;the Transwell method was used to detect cell invasion ability;cell counting kit-8(CCK-8)test was used to detect cell proliferation.Results The expression levels of miR-34a-5p in PANC-1 group,PANC-1/mock group,PANC-1/miR-34a-5p group and PANC-1/miR-34a-5p+gemcitabine group were 1.01±0.08,1.03±0.06,2.43±0.15 and 1.76±0.21;the levels of E-cadherin were 0.61±0.12,0.63±0.08,0.24±0.15 and 0.48±0.05;the levels of Vimentin were 0.56±0.34,0.58±0.29,1.08±0.19 and 0.82±0.11;the relative cell migration levels were(41.48±4.94),(42.97±6.45),(81.42±6.85)and(63.54±7.63)distance·μm-1;the number of invasive cells were 212.62±9.80,209.46±13.67,463.83±35.22 and 325.46±28.44;the survival rates were(13.28±5.24)％,(14.37±4.79)％,(46.15±11.83)％and(35.78±9.42)％.The above indicators in the PANC-1/miR-34a-5p group showed statistically significant differences compared to the PANC-1 and PANC-1/mock groups(all P＜0.05).Conclusion Overexpression of miR-34a-5p promotes EMT of pancreatic cancer cells,migration of pancreatic cancer cells,invasion of pancreatic cancer cells,and chemotherapy resistance of pancreatic cancer cells.

Objective To explore the impact of subclinical hypothyroidism (SCH) complicating hyperu-ricemia (HUA) on carotid atherosclerosis,and to provide reference for the clinical management of the patients with SCH complicating HUA.Methods A retrospective analysis was conducted on the clinical data of 387 in-patients with carotid atherosclerosis in the Department of General Medicine of the Affiliated Hospital of Qing-dao University from January 1,2016,to December 31,2022.The patients were divided into the SCH complica-ting HUA group (n=170),SCH group (n=108),and HUA group (n=109) according to clinical diagnosis results,and into the low risk group (n=137),medium risk group (n=116),high risk group (n=66),and ex-tremely high risk group (n=68) for carotid atherosclerosis according to the carotid ultrasound results.The clinical data were compared among the groups,and the multivariable ordered logistic regression model was used to analyze the influencing factors of carotid atherosclerosis risk degree.Results There were statistically significant differences in gender,BMI,smoking history,drinking history,blood uric acid,thyroid-stimulating hormone (TSH),free triiodothyronine (FT3),free thyroxine (FT4) levels and composition of carotid athero-sclerosis risk degree among the SCH complicating HUA group,SCH group and HUA group (P<0.05).The other indicators had no statistical difference (P>0.05).The age,history of hypertension,history of stroke,blood uric acid,TSH and FT3 levels had statistical differences among the low,medium,high and extremely high risk groups for carotid atherosclerosis (P<0.05).Further pairwise comparison between groups showed that the TSH level in the carotid atherosclerosis low risk group was significantly lower than that in the high and ex-tremely high risk group (P<0.001).The multivariable ordered logistic regression analysis results showed that in-crease of blood uric acid (OR=1.003,95％CI:1.001-1.005,P=0.001),TSH (OR=1.231,95％CI:1.128-1.343,P<0.001) and fasting plasma glucose levels (OR=1.447,95％CI:1.109-1.889,P=0.007),and age in-crease (OR=1.039,95％CI:1.020-1.058,P<0.001) were associated with the increase of carotid atherosclerosis risk.Low-density lipoprotein cholesterol (LDL-C) and total cholesterol showed collinearity,and logistic regression a-nalysis results after principal component analysis transformation showed that the elevated LDL-C level increased the risk of carotid atherosclerosis (OR=1.104,95％CI:1.001-1.218,P<0.001).Conclusion SCH complicating HUA could promote the occurrence of carotid atherosclerosis.TSH,blood uric acid,fasting plasma glucose,LDL-C and age are the independent influencing factors for carotid atherosclerosis risk in patients with SCH complicating HUA.

Objective To detect the expression changes of interleukin-10(IL-10)and transforming growth factor-β1(TGF-β1)during the development of deep vein thrombosis in mice,and to explore the application value of them in thrombus age estimation.Methods The mice in the experimental group were subjected to ligation of inferior vena cava.The mice were sacrificed by excessive anesthesia at 1 d,3 d,5 d,7 d,10 d,14 d and 21 d after ligation,respectively.The inferior vena cava segment with thrombosis was extracted below the ligation point.The mice in the control group were not ligated,and the inferior vena cava segment at the same position as the experimental group was extracted.The ex-pression changes of IL-10 and TGF-β1 were detected by immunohistochemistry(IHC),Western blot-ting and real-time qPCR.Results IHC results revealed that IL-10 was mainly expressed in monocytes in thrombosis and TGF-β1 was mainly expressed in monocytes and fibroblast-like cells in thrombosis.Western blotting and real-time qPCR showed that the relative expression levels of IL-10 and TGF-β1 in each experimental group were higher than those in the control group.The mRNA and protein levels of IL-10 reached the peak at 7 d and 10 d after ligation,respectively.The mRNA expression level at 7 d after ligation was 4.72±0.15 times that of the control group,and the protein expression level at 10 d after ligation was 7.15±0.28 times that of the control group.The mRNA and protein levels of TGF-β1 reached the peak at 10 d and 14 d after ligation,respectively.The mRNA expression level at 10 d after ligation was 2.58±0.14 times that of the control group,and the protein expression level at 14 d after ligation was 4.34±0.19 times that of the control group.Conclusion The expressions of IL-10 and TGF-β1 during the evolution of deep vein thrombosis present time-dependent sequential changes,and the expression levels of IL-10 and TGF-β1 can provide a reference basis for thrombus age estimation.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.