Historical Evolution and Clinical Application of Huanglian Ejiaotang / 中国实验方剂学杂志

ObjectiveTo review the ancient and modern literature of Huanglian Ejiaotang and learn about the historical evolution and clinical application， thereby providing a theoretical basis for the modern application of the classical prescription. MethodLiterature in the Chinese Medical Classics Database was retrieved with "Huanglian Ejiaotang" as the keyword. In China National Knowledge Infrastructure （CNKI） and PubMed， "Huanglian Ejiaotang" in Chinese and English was used as the keyword to retrieve literature. The items and modern clinical application studies related to the prescription， medicine， dosage， syndrome， and treatment of Huanglian Ejiaotang were selected and recorded. The inclusion and exclusion criteria were used to screen out literature. The information about the dynasty， book title， function， and indication was integrated to understand the history， evolution， and clinical application of Huanglian Ejiaotang. ResultFinally， 89 ancient books were included with 111 items. Huanglian Ejiaotang was initially recorded in ZHANG Zhongjing's Treatise on Cold Damage and Miscellaneous Diseases in the Han dynasty. It was composed of five herbs， namely Coptidis Rhizoma， Scutellariae Radix， Paeoniae Radix Alba， Asini Corii Colla， and egg yolk. With the change of historical dynasties， the composition， origin basis， dosage， and preparation method of Huanglian Ejiaotang all changed， but the changes in the processing were not obvious， which was basically consistent with Treatise on Cold Damage and Miscellaneous Diseases. In addition， 48 studies were included to analyze the clinical application of Huanglian Ejiaotang， which was mainly used for insomnia， anxiety， depression， diabetes， and so on. ConclusionAccording to the ancient and modern literature， the origin basis， dosage， processing， decoction， administration， and other content of Huanglian Ejiaotang are consistent with Treatise on Cold Damage and Miscellaneous Diseases. The present clinical application has expanded the usage scale of the ancient record， which promotes the innovation and development of the classic prescription and provides references for later research， development， and accurate application.

The total synthesis of natural cyclopeptide auyuittuqamide A / 药学实践杂志

Objective To synthesize the natural cyclopeptide auyuittuqamide A by Fmoc-based solid phase linear synthesis and liquid phase cyclization. Methods Using 2-chlorotriphenylmethyl chloride (CTC) resin as the solid support, 1,3-diisopropylcarbodiimide (DIC) and 1-hydroxybenzotriazole (HOBt) as the condensing agents, 9-fluorenylmethoxycarbonyl (Fmoc) to protect amino acids were assembled in sequence, and then the linear peptide bearing the protected groups was obtained in presence of trifluoroethanol (TFE) cutting reagent. The protected linear peptide was cyclized with the aid of benzotriazole hexafluorophosphate (PyBOP) and 1-hydroxybenzotriazole (HOBt) in dichloromethane (DCM) solution, followed by trifluoroacetic acid (TFA) deprotection to obtain the cyclic peptide, auyuittuqamide A that was purified by preparative HPLC and characterized by HR-MS and 500MHz 1H-NMR. Results The purity of auyuittuqamide A was more than 95% and the total yield was 5.48%. Conclusion This method has simple synthesis steps and high yield. It is the first to establish a fully synthesis method for the natural cyclic peptide auyuittuqamide A, which lays the foundation for further research of auyuittuqamide A.

Realization and Clinical Study of Robotic Technology in Cardiovascular Interventional Surgery / 中国医疗器械杂志

The high incidence of cardiovascular diseases is a serious threat to human health, and endovascular surgery has become the standard treatment for most interventional cardiovascular diseases. The robotassisted endovascular surgery system further enhances surgeons' ability to perform minimally invasive endovascular procedures in interventional cardiology. This study presents a new robotic technique for coronary intervention from the perspective of clinical application. Aiming at clinical application scenarios, this scheme proposed an intuitive guide wire catheter mechanism design, which accurately and perfectly simulates the doctor's hand movements, realizes the positive and negative direction translation of the guide wire catheter, accurate torque control of the guide wire rotation and locking. The results of animal test showed that the R-OneTM has a high degree of dexterity, accuracy and stability,and meets the clinical needs.

Analysis of genomic information and biological characteristics of a bacteriophage against methicillin-resistant Staphylococcus aureus in patients with median sternal incision infection / 中华烧伤杂志

Objective: To isolate and purify a bacteriophage against methicillin-resistant Staphylococcus aureus (MRSA), and to analyze its genomic information and biological characteristics. Methods: The experimental research methods were adopted. MRSA (hereinafter referred to as host bacteria) solution was collected from the wound of a 63-year-old female patient with the median sternum incision infection admitted to the Second Affiliated Hospital of Army Medical University (the Third Military Medical University). The bacteriophage, named bacteriophage SAP23 was isolated and purified from the sewage of the Hospital by sewage co-culture method and double-layer agar plate method, and the plaque morphology was observed. The morphology of bacteriophage SAP23 was observed by transmission electron microscope after phosphotungstic acid negative staining. The whole genome of bacteriophage SAP23 was sequenced with NovaSeq PE15 platform after its DNA was prepared by sodium dodecyl sulfonate/protease cleavage scheme, and genomic analysis including sequence assembly, annotation, and phylogenetic tree were completed. The bacteriophage SAP23 solution was co-incubated with the host bacterial solution for 4 h at the multiplicity of infection (MOI) of 10.000 0, 1.000 0, 0.100 0, 0.010 0, 0.001 0, and 0.000 1, respectively, and then the bacteriophage titer was measured by the drip plate method to select the optimal MOI, with here and the following sample numbers of 3. The bacteriophage SAP23 solution was co-incubated with the host bacterial solution at the optimal MOI for 5, 10, and 15 min, respectively, and the bacteriophage titer was measured by the same method as mentioned above to select the optimal adsorption time. After the bacteriophage SAP23 solution was co-incubated with the host bacterial solution at the optimal MOI for the optimal adsorption time, the bacteriophage titers were measured by the same method as mentioned above at 0 (immediately), 5, 10, 15, 20, 30, 40, 50, 60, 80, 100, and 120 min after culture, respectively, and a one-step growth curve was drawn. The bacteriophage SAP23 solution was incubated at 4, 37, 50, 60, 70, and 80 ℃ and pH 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 for 1 h, respectively, to determine its stability. A total of 41 MRSA strains stored in the Department of Microbiology of Army Medical University (the Third Military Medical University) were used to determine the host spectrum of bacteriophage SAP23. Results: The bacteriophage SAP23 could form a transparent plaque on the host bacteria double-layer agar plate. The bacteriophage SAP23 has a polyhedral head with (88±4) nm in diameter and a tail with (279±21) nm in length and (22.6±2.6) nm in width. The bacteriophage SAP23 has a linear, double-stranded DNA with a full length of 151 618 bp and 11 681 bp long terminal repeats sequence in the sequence ends. There were 220 open reading frames predicted and the bacteriophage could encode 4 transfer RNAs, while no resistance genes or virulence factors were found. The annotation function of bacteriophage SAP23 genes could be divided into 5 groups. The GenBank accession number was MZ427930. According to the genomic collinearity analysis, there were 5 local collinear blocks in the whole genome between the bacteriophage SAP23 and the chosen 6 Staphylococcus bacteriophages, while within or outside the local collinear region, there were still some differences. The bacteriophage SAP23 belonged to the Herelleviridae family, Twortvirinae subfamily, and Kayvirus genus. The optimal MOI of bacteriophage SAP23 was 0.010 0, and the optimal adsorption time was 10 min. The bacteriophage SAP23 had a latent period of 20 min, and a growth phase of 80 min. The bacteriophage SAP23 was able to remain stable at the temperature between 4 and 37 ℃ and at the pH values between 4 and 9. The bacteriophage SAP23 could lyse 3 of the 41 tested MRSA strains. Conclusions: The bacteriophage SAP23 is a member of the Herelleviridae family, Twortvirinae subfamily, and Kayvirus genus. The bacteriophage SAP23 has a good tolerance for temperature and acid-base and a short latent period, and can lyse MRSA effectively. The bacteriophage SAP23 is a new type of potent narrow-spectrum bacteriophage without virulence factors and resistance genes.

Connective tissue diseases and the liver injury / 中华肝脏病杂志

Connective tissue disease (CTD) are closely related to liver abnormality. CTD can affect the liver causing various degrees of liver injury, coexist with other liver diseases, especially autoimmune liver disease (ALD). Medications for CTD can also lead to liver injury or reactivate the hepatitis B virus. CTD patients can also be positive for ALD-related autoantibodies without corresponding manifestation; and vis versa. The diagnosis and differential diagnosis should be made on integrating clinical presentation, laboratory, imaging, and histological studies, not solely relying on autoantibody positivity.

Chemical constituents of Scrophulariae Radix and their antitumor activities in vitro / 中国中药杂志

The present study investigated the chemical constituents of Scrophulariae Radix and their antitumor activities in vitro. The compounds in the ethyl acetate extract were separated and purified by conventional column chromatographies(such as silica gel, Sephadex LH-20, and ODS column) and semi-preparative high-performance liquid chromatography(HPLC), and their structures were identified by various spectral techniques such as nuclear magnetic resonance(NMR) and mass spectrometry(MS). Twenty-three compounds were isolated and identified as benzyl-β-D-(3',6'-di-O-acetyl) glucoside(1), 5-O-p-methoxybenzoyl kojic acid(2), 5-O-methoxybenzoyl kojic acid(3), 7-O-methylbenzoyl kojic acid(4), 5-O-benzoyl kojic acid(5), methyl ferulate ethyl ether(6), trans-ferulic acid(7), trans-isoferulic acid(8), trans-caffeic acid(9), trans-caffeic acid methyl ester(10), caffeic acid ethyl ester(11), trans-cinnamic acid(12), trans-p-methoxycinnamic acid(13), trans-p-hydroxycinnamic acid(14), trans-p-hydroxycinnamic acid methyl ester(15), 2-(3,4-dihydroxyphenethyl) alcohol(16),(p-hydroxyphenyl) propanoic acid(17), coniferaldehyde(18), sinapaldehyde(19), benzyl β-primeveroside(20), 5-(hydroxymethyl) furfural(21), furan-2-carboxylic acid(22), and decanedioic acid(23). Among them, compound 1 is a new benzyl glucoside, compounds 2-4 are new pyranone compounds, compound 5 is a new natural product of pyranone. The NMR data of compounds 5 and 6 are reported for the first time. Compounds 6 and 20 were isolated from the Scrophularia plant for the first time. Compounds 8, 11, 14, 16, 18, 19, 22, and 23 were isolated from this plant for the first time. The in vitro cytotoxic activities of these compounds against three tumor cell lines(HepG2, A549, and 4 T1) were evaluated. The results showed that compounds 10 and 15 showed cytotoxic activities against HepG2 cells with IC_(50) values of(19.46±0.48) μmol·L~(-1) and(46.10±1.21) μmol·L~(-1).

Warming acupuncture combined with "three steps and seven methods" of tuina for chronic nonspecific low back pain of yang deficiency and cold-dampness blockage: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical efficacy and possible mechanism of warming acupuncture combined with "three steps and seven methods" of tuina and simple "three steps and seven methods" of tuina in treatment of chronic nonspecific low back pain (NLBP) of yang deficiency and cold-dampness blockage.@*METHODS@#A total of 138 patients were randomized into an observation group (69 cases, 5 cases dropped off) and a control group (69 cases, 7 cases dropped off). In the control group, "three steps and seven methods" of tuina was applied. On the basis of the treatment in the control group, warming acupuncture was applied at Shenshu (BL 23), Yaoyangguan (GV 3), Mingmen (GV 4), Weizhong (BL 40) and ashi points. The treatment was given once a day, 6 times a week for 3 weeks in both groups. Before and after treatment, the short form of McGill pain questionnaire (SF-MPQ) score, Oswestry disability index (ODI) score, finger-to-floor distance (FFD), Schober test distance, fear-avoidance beliefs questionnaire (FABQ) score and yang deficiency and cold-dampness blockage score were observed, the serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and thromboxane B2 (TXB2) were detected in both groups. The recurrence rate was evaluated in follow-up of 6 months after treatment.@*RESULTS@#After treatment, the scores of PRI, PPI, VAS, ODI, FABQ and FFD, yang deficiency and cold-dampness blockage scores were decreased compared before treatment in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01); the Schober test distances were increased compared before treatment in both groups (P<0.01), and that in the observation group was larger than the control group (P<0.01). After treatment, the serum levels of TNF-α, IL-1β, IL-6 and TXB2 were decreased compared before treatment in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01). In follow-up, the recurrence rate was 12.8% (6/47) in the observation group, which was lower than 34.3% (12/35) in the control group (P<0.05).@*CONCLUSION@#Warming acupuncture combined with "three steps and seven methods" of tuina can effectively alleviate pain in patients with chronic NLBP of yang deficiency and cold-dampness blockage, improve activity and dysfunction of waist, the clinical efficacy is superior to simple "three steps and seven methods" of tuina, its mechanism may be relate to the inhibition of inflammatory reaction.

Effect of electroacupuncture and pretreatment of electroacupuncture on pain sensitization and expression of P2X7R in spinal dorsal horn in rats with diabetic neuropathic pain / 中国针灸

OBJECTIVE@#To observe the occurrence time of neuralgia and the expression of purinergic ligand-gated ion channel 7 receptor (P2X7R) in the dorsal horn of the spinal cord after intraperitoneal injection of streptozotocin (STZ) in diabetic rats, and to explore the effect of electroacupuncture (EA) and pretreatment of EA on the heat pain threshold and expression of P2X7R in the spinal dorsal horn in rats with diabetic neuropathic pain (DNP), and to explore the possible mechanism of EA for DNP.@*METHODS@#PartⅠ: Thirty male SD rats were randomly selected from 64 male SD rats as the control group; the remaining rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model, and 30 rats were successfully modeled as the model group. The control group and the model group were divided into three subgroups respectively at 7, 14 and 21 days, with 10 rats in each subgroup. Body mass, fasting blood glucose (FBG) and thermal pain threshold were recorded at 7, 14 and 21 days after injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot. PartⅡ: Eight SD rats were randomly selected from 35 male SD rats as the blank group, and the remaining 27 rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model. The 24 rats with successful diabetes model were randomly divided into a DNP group, an EA group and a pre-EA group, 8 rats in each group. Fifteen to 21 days after STZ injection, the EA group received EA at "Zusanli" (ST 36) and "Kunlun" (BL 60), continuous wave, frequency of 2 Hz, 30 min each time, once a day; the intervention method in the pre-EA group was the same as that in the EA group. The intervention time was 8 to 14 days after STZ injection. The body mass, FBG and thermal pain threshold were recorded before STZ injection and 7, 14 and 21 days after STZ injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot 21 days after injection.@*RESULTS@#PartⅠ: Compared with the control group, in the model group, the body mass was decreased and FBG was increased 7, 14 and 21 days after STZ injection (P<0.01), and the thermal pain threshold was decreased 14 and 21 days after STZ injection (P<0.05), and the expression of P2X7R in spinal dorsal horn was increased 7, 14 and 21 days after STZ injection (P<0.05, P<0.01). PartⅡ: Compared with the blank group, in the DNP group, the body mass was decreased and fasting blood glucose were increased 7, 14 and 21 days after STZ injection (P<0.01). Compared with the DNP group, in the pre-EA group, the heat pain threshold was increased 14 and 21 days after STZ injection (P<0.05), while in the EA group, the heat pain threshold was increased 21 days after STZ injection (P<0.01), and the expression of P2X7R in the dorsal horn in the EA group and the pre-EA group was decreased (P<0.01).@*CONCLUSION@#The diabetic neuropathic pain is observed 14 days after STZ injection. EA could not only treat but also prevent the occurrence of DNP, and its mechanism may be related to down-regulation of P2X7R expression in the dorsal horn of the spinal cord.

Research advances in animal models of Wilson's disease / 临床肝胆病杂志

Wilson's disease (WD) is a rare autosomal recessive disorder with a complex pathogenesis involving multiple systems, multiple visceral organs, and the complex copper homeostasis regulation system within the body. The liver is the most common organ for copper deposition, and liver injury is the earliest and most common manifestation of WD; therefore, it is important to find an ideal animal model for WD research. By summarizing the animal models of WD commonly used in the world, this article systematically summarizes the background, liver and nervous manifestations, and application of different models and compares the characteristics of different animal models, so as to provide a reference for the application of various animal models of WD.

Correlation between children and adolescents physical activity and socioeconomic status in China / 中国学校卫生

Objective@#To understand the correlation between physical activity (PA) and socioeconomic status (SES) among Chinese children and adolescents, and to provide theoretical basis for physical activity promotion for Chinese children and adolescents.@*Methods@#By using stratified random cluster sampling, a total of 4 269 children and adolescents aged 7 to 18 were selected from six cities in China from September to December 2018. Physical Activity Level Evaluation Questionnaire of Chinese Children and Adolescents Aged 7 to 18 was used to investigate PA and SES, and the height and weight were measured.@*Methods@#In terms of different intensity of PA, the time spent on light intensity physical activity(LPA), moderate intensity physical activity(MPA), moderate to vigorous physical activity(MVPA)and total physical activity(TPA) in low SES group was 28.5(6.9,57.1) min/d, 46.2 (25.7,79.2) min/d, 61.4(34.3,101.9) min/d and 102.9(65.0,145.8)min/d respectively, which was higher than that in middle SES groups [ 21.4 (4.3,50.7), 37.1(18.6,65.7), 50.3(27.1,86.8), 85.7(49.3,127.1) min/d] and high SES groups [24.3( 5.0 ,54.3), 40.0(21.4,69.1), 54.3(32.9,91.4), 89.6(55.7,132.9) min/d]( P <0.01). In terms of different types of PA, the traffic PA [40.0(15.0,68.6) min/d] and entertainment PA[4.3(0,17.1)min/d] accounted the highest proportion in low SES group,while sports PA [36.4(20.7,60.7) min/d] accounted the highest proportion in high SES group( P <0.01).The compliance rates of MVPA in low, middle and high SES groups were 51.1%, 42.5% and 45.2%, respectively, and the differences were statistically significant ( χ 2= 22.02 , P <0.05). After controlling for confounding factors, the detection rate of MVPA in the low SES group was 1.24 times higher than that in the high SES group ( P <0.01).@*Conclusion@#The MVPA and TPA time of children and adolescents with middle SES group were the lowest. Physical activities spent on traffic and entertainment account highest in low SES group, while physical activities spent on sports account highest in high SES group.

Generation and phenotype of myeloid cell specific Clcn7-mutation osteopetrosis mouse model / 中华内分泌代谢杂志

Objective:To construct a myeloid cell specific Clcn7-G763R mutant mouse model and characterize its phenotype.Methods:A mouse conditional knocked in p. G763R mutation in Clcn7 gene was constructed and bred with LysM cre mice to obtain osteopetrosis mice with myeloid cell specific Clcn7-G763R mutation. The differences of bone mass in mice with different genotypes were analyzed using Micro CT and the changes of histology were observed with HE staining. Osteoclasts were cultured and the expression levels of osteoclasts differentiation and maturation-related genes were detected by real-time PCR. The functions of osteoclasts were examined through bone resorption assay.Results:The body weight of homozygous mutant mice at 4 weeks old was reduced compared with the wild type mice [(12.000±1.666)g vs(15.630±2.314)g, P=0.021], with shorter femur length [(1.160±0.096)cm vs (1.300±0.082)cm, P=0.037]. Micro CT showed that bone mineral density of homozygous mutant mice was remarkably increased at 4 weeks old [(0.753±0.002)g/cm 3vs(0.143±0.034)g/cm 3, P=0.003], while bone mineral density of heterozygous mutant mice increased significantly at 8 weeks old [(0.236±0.021)g/cm 3vs(0.180±0.020)g/cm 3, P=0.030]. HE staining revealed increased trabecula bone volume in the mutant mice, especially in homozygous mutant mice with narrow bone marrow cavity and wider hypertrophic zone of chondrocytes. There was no significant difference in the number of osteoclasts between wild type mice and heterozygous mice in vitro( P=0.358), while total area of osteoclasts increased in heterozygous mutant mice [(3.590×10 6±0.911×10 6)μm 2vs(1.352×10 6±0.260×10 6)μm 2, P=0.043]. Impaired function of resorption was unveiled by bone resorption assay. There were no significant differences in the expressions of osteoclast differentiation and maturity-related genes including NFATc1, c-fos, Ctsk, and Acp5 between the two groups. Conclusion:A myeloid cell specific Clcn7-G763R mutation mice with impaired osteoclasts and increased bone mass is successfully constructed.

Efficay of different doses of remimazolam for anesthesia induction during reoperation in asthenic patients with tracheotomy / 中华麻醉学杂志

Objective:To evaluate the efficay of different doses of remimazolam for anesthesia induction during reoperation in asthenic patients with tracheotomy.Methods:One hundred and twenty patients of both sexes, aged 19-64 yr, with a modified frailty index score ≥3, of American Society of Anesthesiologists physical status Ⅳ, scheduled for reoperation after tracheotomy, were divided into 4 groups ( n=30 each)using a random number table method: propofol group (group C) and different doses of remimazolam groups (R 1, R 2 and R 3 groups). Anesthesia was induced with intravenous sufentanil 5 μg, propofol 1.5 mg/kg in group C and with remimazolam 0.1, 0.2 and 0.3 mg/kg in R 1, R 2 and R 3 groups, respectively.The tracheotomy cannula was replaced with a reinforced endotracheal intubation (ID=6.0 mm) when bispectral index value ≤ 65.Mean arterial pressure and heart rate were recorded before induction (T 0), immediately before replacement of the tube (T 1) and immediately after replacement of the tube (T 2). The onset time of anesthesia and adverse reactions such as hypotension, bradycardia and bucking during replacement of the tube, and requirement for rescue sedation were recorded. Results:Compared with group C, mean arterial pressure was significantly increased at T 1, 2 in group R 1 and group R 2, the onset time of anesthesia was significantly prolonged, the incidence of hypotension and bradycardia was decreased in R 1, R 2 and R 3 groups, and the requirement for rescue sedation in group R 1 and incidence of bucking in group R 1 and group R 2 were increased ( P<0.05 or 0.01). Compared with group R 1, heart rate at T 2 was significantly decreased, the onset time of anesthesia was shortened, and the requirement for rescue sedation and incidence of bucking were decreased in C, R 2 and R 3 groups, and the incidence of hypotension was significantly increased in group R 3 ( P<0.05 or 0.01). Compared with group R 2, the onset time of anesthesia was significantly shortened in group R 3 ( P<0.05). Conclusions:Remimazolam 0.2 mg/kg provides good efficacy when used for anesthesia induction with fewer side effects during reoperation in asthenic patients with tracheotomy.

Monitoring of sunitinib blood concentration and analysis of its safety and efficacy in Chinese patients with metastatic renal cell carcinoma / 中华泌尿外科杂志

Objective:To investigate the safety and efficacy of individualized sunitinib schedule for patients with metastatic renal cell carcinoma (mRCC) according to the monitoring results of plasma drug concentration.Methods:The clinical data of patients with mRCC who received sunitinib treatment in our center from January 2014 to December 2020 were retrospectively analyzed, including 20 patients who underwent monitoring of plasma drug concentration (monitoring group), and 45 patients, matched by propensity score matching, received sunitinib but did not undergo monitoring of plasma drug concentration during the same period (unmonitored group). In the monitoring group, there were 12 males and 8 females. The mean age was 52.9 years, and ECOG score ≤1 in 16 cases (80%). Three patients were in the IMDC favorable-risk group, 15 patients were in the intermediate-risk group, and 2 patients were in the high-risk group. There were 18 cases of clear cell carcinoma and 2 cases of non-clear cell carcinoma, 5 cases of ISUP grade 1-2 and 11 cases of grade 3-4. In the unmonitored group, there were 31 males and 14 females. The mean age was 57.7 years, and 30 patients had ECOG score ≤1, 15 cases ≥2. There were 10 cases in IMDC favorable-risk group, 23 cases in intermediate-risk group, and 12 cases in high-risk group. Thirty-seven cases were clear cell carcinoma and 8 cases were non-clear cell carcinoma, 8 cases were in ISUP grade 1-2 and 28 cases in grade 3-4. There were no statistically significant differences between the two groups in the above parameters ( P>0.05). The monitoring group used the regimen of taking sunitinib for 4 weeks and stopping for 2 weeks (4/2 week) in the first cycle. The blood concentration of sunitinib was monitored before the first cycle and on days 4, 7, 10, 14, 21 and 28, and personalized medication plan was formulated according to the curve of the blood concentration. The 4/2 week scheme was adopted in the undetected monitoring group.The two groups were compared in the incidence of adverse events (AEs), progression-free survival (PFS), overall survival (OS), tumor treatment response and other clinical outcomes. Results:In the monitoring group, 90% (18/20) of patients receiving sunitinib had a steady-state plasma concentration of more than 150ng/ml, of which 10 patients (50%) had a plasma concentration of 150-200 ng/ml and 8 patients (40%) had a plasma concentration of more than 200 ng/ml. Meanwhile, all patients with plasma concentration higher than 150 ng/ml developed severe AEs (grade 3 and above) after treatment. The other two patients' plasma concentration were 100-150 ng/ml, and did not have severe AEs.All patients in the monitoring group received individualized medication schedule adjustment according to the plasma drug concentration and the occurrence point of severe AEs, ensuring that the peak plasma drug concentration was maintained at about 100-150 ng/ml. Among them, 6 patients were changed to take 2 weeks and stop for 1 week (2/1 week schedule), 4 patients were changed to take 10 days and stop for 5 days (10/5 d schedule), 7 patients were changed to take 7 days and stop for 3 days (7/3 d schedule), and 3 patients were changed to take 5 days and stop for 2 days (5/2 d schedule). The incidence of severe AEs significantly decreased from 90% (18/20) to 35% (7/20), and the difference was statistically significant ( P=0.003), while the incidence of grade 3 and higher AEs was 55.6% (25/45) in the standard group, which was statistically significant compared with the incidence of severe AEs before adjustment in the monitoring group ( P=0.006). Further analysis of the efficacy difference between the two groups showed that the overall objective response rate in the monitoring group (40%, 8/20) was higher than that in the standard group (20%, 9/45), although the difference was not statistically significant ( P=0.09). Median PFS and OS were significantly longer in the monitored group than in the standard group (PFS: 23 vs. 10 months, P=0.002; OS: not reached vs.25 months, P=0.005). Conclusions:The bioavailability of sunitinib is high in mRCC patients, which may lead to higher plasma drug concentration, adjustment of medication regimen based on blood concentration monitoring significantly improved patient safety and clinical outcomes. However, further validation by larger-scale, multi-center and prospective studies is needed.

Research progress on drug resistance mechanism and treatment of Stenotrophomonas maltophilia / 中华临床感染病杂志

Stenotrophomonas maltophilia is a gram-negative bacillus which widely exists in natural and hospital environment, and it is also one of the common opportunistic pathogens in clinical settings. The virulence and pathogenicity of Stenotrophomonas maltophilia are weak, however, due to resistance to a variety of antibacterial drugs, it can cause bloodstream infections or pneumonia in immunocompromised or critically ill patients, leading to poor prognosis. Moreover, the inherent drug resistance and increasing acquired drug resistance may make the treatment of the first line antibiotics, like trimethoprim-sulfamethoxazole or quinolone ineffective. Therefore, it is important to understand the drug resistance mechanism and the main countermeasures for it. In this article, the research progress on drug resistance mechanism and treatment for Stenotrophomonas maltophilia are reviewed.

Relationship between the high sensitivity C-reactive protein and anxiety levels in hospitalized patients with cardiovascular-related diseases and hypertension / 中华健康管理学杂志

Objective:To analyze the relationship between the high sensitivity C-reactive protein (hs-CRP) and anxiety levels in patients hospitalized with cardiovascular-related diseases and hypertension.Methods:A total of 221 patients hospitalized with cardiovascular-related diseases in the Fuwai Hospital were selected by a voluntary sampling method from September to December 2021. Participants were divided into hypertensive and non-hypertensive groups ( n=119 and n=102) based on the diagnosis of hypertension in their inpatient medical records. Anxiety levels were assessed using the Zung Self-Rating Anxiety Scale, and the levels of serum hs-CRP were estimated by automatic immunoanalyzer. Multivariate logistic regression was used to analyze the relationship between hs-CRP and anxiety. Results:In the hypertensive group, the risk of anxiety in patients with abnormal hs-CRP (>3 mg/L) was 4.239 times (95% CI: 1.569-11.748, P=0.005) higher than those in normal hs-CRP (≤3 mg/L). In turn, compared with patients without anxiety, those with anxiety had 3.878 times greater probability of experiencing abnormal hs-CRP (95% CI: 1.495-10.062, P=0.005), while those with mild anxiety and moderate to severe anxiety had 4.525 times (95% CI: 1.392-14.714, P=0.012) and 3.286 times (95% CI: 0.911-11.357, P=0.070) greater odds of experiencing abnormal hs-CRP, respectively. No similar significant association was seen in the non-hypertensive group. Conclusion:There is an interrelationship between elevated hs-CRP and anxiety in hospitalized patients with cardiovascular-related diseases and hypertension.

Serially evaluation of changes in myocardial perfusion, hibernation myocardium and left ventricular function in the development of chronic coronary artery occlusion by gated SPECT perfusion and gated PET imaging in pigs / 中华核医学与分子影像杂志

Objective:To serially characterize the myocardial perfusion, myocardial hibernation and left ventricular (LV) function as well as LV remodeling in progressive coronary artery stenosis in Chinese mini-pigs.Methods:In 8 Chinese mini-pigs (5 males, 3 females; age: 10 months), chronic progression of coronary stenosis and finally occlusion was established using Ameroid constrictor implantation at the 1 cm below the bifurcation of the first diagonal branch of the left anterior descending (LAD) artery. Serial gated 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT/CT, gated 18F-FDG PET/CT imaging and coronary angiography (CAG) were performed before surgery and at the 1st, 4th and 8th week after surgery. Longitudinally, total perfusion defect (TPD), LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), summed motion score (SMS), summed thickening score (STS) and hibernating myocardium (HM) were analyzed. Repeated measures analysis of variance, Kruskal-Wallis rank sum test and Bonferroni correction method were used to analyze data. Results:One mini-pig died of infection after the Ameroid constrictor implantation. In the remaining 7 mini-pigs, TPD was progressively increased with time prolonged (0, 12.0%(0, 33.0%), (41.1±23.7)% and (49.3±24.5)%; H=17.03, P=0.001); Compared with HM before the surgery (100%), HM was gradually reduced from the 1st (21.0%(6.0%, 100%)) to the 4th (18.0%(3.0%, 33.0%)) week after surgery, and then increased to the 8th week after surgery ((23.0±15.4)%; H=13.09, P=0.004), but there was no significant difference between the 1st and 4th week, or between the 4th and 8th week after surgery (both P>0.05 (Bonferroni correction method)). Accordingly, LVEF gradually decreased ((73.7±8.4)%, (63.7±19.1)%, (53.7±14.6)% and (49.9±15.4)%; F=6.22, P=0.004). LVEDV (9.0(6.0, 21.0), (31.4±16.3), (32.9±17.4) and (36.4±17.5) ml; H=8.58, P=0.035)and LVESV ((3.8±3.2), (15.9±15.3), 12.0(10.0, 17.0)and (19.3±10.9) ml; H=10.51, P=0.015) gradually increased. SMS and STS continuously increased as well ( H values: 16.49, 13.33, P values: 0.001, 0.004). Conclusions:With the progression of coronary artery stenosis to occlusion, myocardial perfusion is gradually decreased, while the global and regional LV function, LV remodeling are gradually aggravated, and HM is gradually reduced. After the chronic coronary artery occlusion, myocardial perfusion has a trend to be improved and HM is gradually recovered.

Combined posteromedial and anterolateral approach for reduction and internal fixation in the treatment of Wahlquist type C medial tibial plateau fracture with coronal subluxation of knee joint / 中华骨科杂志

Objective:To compare the efficacy of posteromedial and anterolateral approach and single posteromedial reversed L approach for reduction and internal fixation in the treatment of Wahlquist type C medial tibial plateau fracture (mTPF) with coronal subluxation of knee joint.Methods:A retrospective analysis was conducted on 44 surgically treated Wahlquist type C mTPFs from January 2010 to April 2021. They were divided into single-approach group (21 cases, 12 males and 9 females with mean age of 50.71±11.28 years) and combined-approach group (23 cases, 16 males and 7 females with mean age of 51.00±10.07 years) according to their surgical approach. The single-approach group contained 14 left limbs and 7 right limbs, and there were 19 anteromedial-posteromedial-posterolateral mTPF and 2 posteromedial-posterolateral mTPF. The combined-approach group contained 18 left limbs and 5 right limbs, and there were 22 anteromedial-posteromedial-posterolateral mTPF and 1 posteromedial-posterolateral mTPF. The intraoperative blood loss and incidence of blood transferring were assessed according to the anesthetic recording. The incidence of residual knee subluxation and articular surface step, medial proximal tibial angle (MPTA) and posterior proximal tibial angle (PPTA) were measured on the postoperative plain radiograph and the function recovery of the affected knee was evaluated by the short musculoskeletal function assessment (SMFA) and the visual analogue scale (VAS).Results:The intraoperative blood loss in combined-approach group was 597.83±89.79 ml and 516.67±79.58 ml in single-approach group, there was a significant difference between the two groups ( t=3.16, P=0.003). The incidence of blood transferring was 17% (4/23) in the combined-approach group and 14% (3/21) in the single-approach group, with no significant difference (χ 2=0.08, P=0.78). All 44 patients were followed up for 8 to 133 months (mean 54 months). The rate of the residual knee subluxation and unsatisfied articular surface reduction in the combined-approach group was lower than that in the single-approach group (34.8% vs. 76.2%, χ 2=7.59, P=0.006; 30.4% vs. 61.9%, χ 2=4.39, P=0.036). There was no significant difference between the combined-approach group and single-approach groups in the postoperative MPTA (86.67°±3.31° vs. 85.86°±4.36°, t=0.88, P=0.386) and PPTA (81.57°±3.22° vs. 83.90°±6.80°, t=1.44, P=0.162). The SMFA and VAS score sin the combined-approach group were significantly better than single-approach groups (20.52±11.04 vs. 31.19±16.79; t=2.51, P=0.016; 2.74±1.32 vs. 3.76±1.04; t=3.13, P=0.007). Conclusion:The efficacy of combined posteromedial and anterolateral approach in the treatment of Wahlquist type C mTPF with coronal subluxation of knee joint is superior to that of traditional single posteromedial reversed L approach.

Effect of BMMSCs on steatosis of DCD donor liver in SD rats by normothermic machine perfusion / 中华肝胆外科杂志

Objective:To investigate the role of ferroptosis in bone marrow mesenchymal stem cells (BMMSCs) combine with normothermic machine perfusion (NMP) in repairing steatotic liver donor after cardiac death (DCD) in SD rats.Methods:BMMSCs were derived from SD rats to establish the DCD model of rats steatotic liver. A total of 24 rats were randomly divided into four groups: simple steatotic liver model group (Sham), static cold storage group (SCS), NMP, BMMSCs combine with NMP preservation group (BNMP), and the preservation time was 4 hours. The donor liver function was evaluated by liver structure, liver enzymes and lactic acid content of perfusion fluid, bile secretion and inflammatory cytokines; furthermore, in order to evaluate the occurrence of liver ferroptosis, the content of Fe 2+, malondialdehyde and glutathione (GSH) in liver tissue, as well as the mRNA or protein expression changes of cyclooxygenase-2 (COX-2), prostaglandin-endoperoxide synthase 2 (Ptgs2), glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) were detected. Results:After DCD steatotic donor liver was preserved for 4 hours, the liver injury, pro-inflammatory and anti-inflammatory cytokines expression in the BNMP and NMP groups were better than those in the SCS group. During the machine perfusion preservation period, alanine aminotransferase [(189.0±12.5)U/L vs. (227.7±16.2)U/L], aspartate aminotransferase [(207.3±18.6)U/L vs. (247.0±11.8)U/L] and lactic acid [(2.3±0.3)mmol/L vs. (2.9±0.2)mmol/L] in the BNMP group is lower than those in NMP group, moreover, the amount of hepatic bile secretion in the BNMP group [(1 245.7±46.8) μl vs. (1 014.3±67.9) μl] was more than that in NMP group, the difference was statistically significant (all P<0.05). The content of Fe 2+ and malondialdehyde in the liver tissue of BNMP group was significantly lower than those of SCS and NMP groups, on the contrary, the content of GSH was significantly higher than those of SCS and NMP groups. In addition, in the BNMP group, the mRNA level of Ptgs2 and protein level of COX-2 in the liver were significantly reduced, and expression of GPX4 and FTH1 were significantly higher than those of NMP and SCS groups, the differences were statistically significant (all P<0.05). Conclusion:BMMSCs combine with normothermic machine perfusion can better repair SD rats DCD steatotic donor liver and its mechanism of action may be related to its regulation on liver ferroptosis.

The value of CT signs combined with radiomics in the differentiation of COVID-19 from other viral pneumonias / 中华放射学杂志

Objective:To explore the classification performance of combined model constructed from CT signs combined with radiomics for discriminating COVID-19 pneumonia and other viral pneumonia.Methods:The clinical and CT imaging data of 181 patients with viral pneumonia confirmed by reverse transcription-polymerase chain reaction in 15 hospitals of Yunnan Province from March 2015 to March 2020 were analyzed retrospectively. The 181 patients were divided into COVID-19 group (89 cases) and non-COVID-19 group (92 cases), which were further divided into training cohort (126 cases) and test cohort (55 cases) at a ratio of 7∶3 using random stratified sampling. The CT signs of pneumonia were determined and the radiomics features were extracted from the initial unenhanced chest CT images to build independent and combined models for predicting COVID-19 pneumonia. The diagnostic performance of the models were evaluated using receiver operating characteristic (ROC) analysis, continuous net reclassification index (NRI) calibration curve and decision curve analysis.Results:The combined models consisted of 3 significant CT signs and 14 selected radiomics features. For the radiomics model alone, the area under the ROC curve (AUC) were 0.904 (sensitivity was 85.5%, specificity was 84.4%, accuracy was 84.9%) in the training cohort and 0.866 (sensitivity was 77.8%, specificity was 78.6%, accuracy 78.2%) in the test cohort. After combining CT signs and radiomics features, AUC of the combined model for the training cohort was 0.956 (sensitivity was 91.9%, specificity was 85.9%, accuracy was 88.9%), while that for the test cohort was 0.943 (sensitivity was 88.9%, specificity was 85.7%, accuracy was 87.3%). The AUC values of the combined model and the radiomics model in the differentiation of COVID-19 group and the non-COVID-19 group were significantly different in the training cohort ( Z=-2.43, P=0.015), but difference had no statistical significance in the test cohort ( Z=-1.73, P=0.083), and further analysis using the NRI showed that the combined model in both the training cohort and the test cohort had a positive improvement ability compared with radiomics model alone (training cohort: continuous NRI 1.077, 95 %CI 0.783-1.370; test cohort: continuous NRI 1.421, 95 %CI 1.051-1.790). The calibration curve showed that the prediction probability of COVID-19 predicted by the combined model was in good agreement with the observed value in the training and test cohorts; the decision curve showed that a net benefit greater than 0.6 could be obtained when the threshold probability of the combined model was 0-0.75. Conclusion:The combination of CT signs and radiomics might be a potential method for distinguishing COVID-19 and other viral pneumonia with good performance.

Comparison of coracoclavicular ligament anatomical reconstruction versus clavicular hook plate in treatment of Neer Ⅱb distal clavicular fractures / 中华创伤骨科杂志

Objective:To compare the clinical efficacy between coracoclavicular ligament anatomical reconstruction and clavicular hook plate in the treatment of Neer Ⅱb distal clavicular fractures.Methods:A total of 64 patients with Neer Ⅱb clavicular fracture were treated at Department of Orthopaedics, The First Affiliated Hospital to Nanjing Medical University from September 2016 to June 2019. They were 35 males and 29 females, aged from 19 to 68 years (average, 50.7 years). They were assigned into 2 groups according to their operative methods: a reconstruction group of 30 cases undergoing coracoclavicular ligament anatomical reconstruction and a hook plate group of 34 cases undergoing fixation with a clavicular hook plate. The 2 groups were compared in terms of hospital stay, operation time, intraoperative blood loss, surgical incision length, postoperative coracoclavicular separation ratio, visual analogue scale (VAS) and Constant-Murley shoulder scores at 3, 6 and 12 months after operation, and postoperative complications.Results:There was no significant difference in general data between the 2 groups, showing comparability between groups ( P>0.05). Operations were completed uneventfully and surgical incisions healed by primary intention in both groups after operation. All the patients were followed up for 12 to 24 months (average, 14.6 months). The operation time [(74.6±22.0) min] and incision length [(10.4±0.4) cm] were significantly shorter but the intraoperative blood loss [(90.2±5.3) mL] was significantly less in the hook plate group than those in the reconstruction group [(95.6±20.8) min, (12.4±0.9) cm and (74.2±3.5) mL] ( P<0.05). There was no significant difference in hospital stay between the 2 groups ( P>0.05). At 3, 6 and 12 months after operation, the VAS scores (1.8±0.5, 1.2±0.3 and 1.1±0.2) and Constant-Murley scores (85.2±4.6, 91.1±2.6 and 92.1±2.2) in the reconstruction group were significantly better than those in the hook plate group (3.2±1.0, 1.6±0.3 and 1.5±0.3; 73.6±2.9, 85.9±4.6 and 87.0±3.1) ( P<0.05). At the last follow-up, the postoperative coracoclavicular separation ratio (elevation) in the hook plate group (0.20±0.16) was significantly greater than that in the reconstruction group (0.10±0.05) ( P<0.05). Conclusion:In the treatment of Neer ⅡB distal clavicular fractures, coracoclavicular ligament anatomical reconstruction may lead to better fixation and fewer postoperative complications than a clavicular hook plate, demonstrating fine clinical efficacy.