Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China / 中西医结合学报

OBJECTIVE@#Omicron, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, is responsible for numerous infections in China. This study investigates the association between the use of Seven-Flavor Herb Tea (SFHT) and the risk of SARS-CoV-2 infection to develop precise and differentiated strategies for control of the coronavirus disease 2019 (COVID-19).@*METHODS@#This case-control study was conducted at shelter hospitals and quarantine hotels in China. A total of 5348 laboratory-confirmed COVID-19 patients were enrolled between April 1 and May 31, 2022, while 2190 uninfected individuals served as healthy controls. Structured questionnaires were used to collect data on demographics, underlying diseases, vaccination status, and use of SFHT. Patients were propensity-score-matched using 1:1 nearest-neighbor matching of the logit of the propensity score. Subsequently, a conditional logistic regression model was used for data analysis.@*RESULTS@#Overall, 7538 eligible subjects were recruited, with an average age of [45.54 ± 16.94] years. The age of COVID-19 patients was significantly higher than that of uninfected individuals ([48.25 ± 17.48] years vs [38.92 ± 13.41] years; t = 22.437, P < 0.001). A total of 2190 COVID-19 cases were matched with uninfected individuals at a 1:1 ratio. The use of SFHT (odds ratio = 0.753, 95% confidence interval: 0.692, 0.820) was associated with a lower risk of SARS-CoV-2 infection compared to untreated individuals.@*CONCLUSION@#Our findings suggest that taking SFHT reduces the risk of SARS-CoV-2 infection. This is a useful study in the larger picture of COVID-19 management, but data from large-sample multi-center, randomized clinical trial are warranted to confirm the finding. Please cite this article as: Zhang SX, Chen XX, Zheng Y, Cai BH, Shi W, Ru M, Li H, Zhang DD, Tian Y, Chen YL. Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China. J Integr Med. 2023; 21(4):369-376.

Inhibitory Effect of Kaempferol on Proliferation of KG1a Cells and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of kaempferol on proliferation of acute myeloid leukemia (AML) KG1a cells and its mechanism.@*METHODS@#Human AML KG1a cells in logarithmic growth stage were taken and set at 25, 50, 75 and 100 μg/ml kaempferol group, another normal control group (complete medium without drug) and solvent control group (add dimethyl sulfoxide) were also set. After 24 and 48 hours of intervention, the cell proliferation rate was detected by CCK-8 assay. In addition, interleukin-6 (IL-6) combined with kaempferol group (Plus 20 μg/l IL-6 and 75 μg/ml kaempferol) was set up, 48 hours after culture, the cell cycle and apoptosis of KG1a cells were detected by flow cytometry, the mitochondrial membrane potential (MMP) of KG1a cells was detected by MMP detection kit (JC-1 method), and the expression of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway related proteins in KG1a cells were detected by Western blot.@*RESULTS@#The cell proliferation rate of 25, 50, 75 and 100 μg/ml kaempferol group decreased significantly (P<0.05), and with the increase of kaempferol dose (r24 h=-0.990, r48 h= -0.999), the cell proliferation rate decreased gradually (P<0.05). The inhibitory effect of 75 μg/ml kaempferol on cell proliferation reached half of effective dose after 48 hours of intervention. Compared with normal control group, the G0/G1 phase cell proportion and apoptosis rate of cells in 25, 50 and 75 μg/ml kaempferol group increased, while the S phase cell proportion, MMP, phosphorylated JAK2 (p-JAK2)/JAK2 and phosphorylated STAT3 (p-STAT3)/STAT3 protein expression decreased in a dose-dependent manner (r=0.998, 0.994, -0.996, -0.981, -0.997, -0.930). Compared with 75 μg/ml kaempferol group, the G0/G1 phase cell proportion and apoptosis rate of cells in IL-6 combined with kaempferol group decreased, while the S phase cell proportion, MMP, p-JAK2/JAK2 and p-STAT3/STAT3 protein expression increased significantly (P<0.05).@*CONCLUSION@#Kaempferol can inhibit KG1a cell proliferation and induce KG1a cell apoptosis, its mechanism may be related to the inhibition of JAK2/STAT3 signal pathway.

Correlation between Serum Homocysteine Level, MTHFR Gene Polymorphism and Patients with Hematological Diseases Complicated with Coronary Heart Disease / 中国实验血液学杂志

OBJECTIVE@#To observe the expression level of serum homocysteine (Hcy) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in patients with hematological diseases complicated with coronary heart disease, and analyze the relationship between serum Hcy level, MTHFR gene polymorphism and coronary heart disease.@*METHODS@#The medical records of 80 patients with coronary heart disease who completed treatment of hematological diseases during the period from March 2018 to March 2020 were selected as observation group. In addition, the medical records of 92 patients with hematological diseases who completed treatment in our hospital during the same period were selected as control group. Venous blood samples of the two groups were collected to detect serum Hcy level and MTHFR gene polymorphism. The serum Hcy levels of the two groups with different MTHFR genotypes were compared, and the effects of the above indicators on hematological diseases complicated with coronary heart disease were analyzed.@*RESULTS@#The detection rates of MTHFR gene TT and TC in the observation group were higher than those in the control group, while the distribution frequency of MTHFR genotype CC was lower (P<0.05). The serum Hcy levels of the patients with MTHFR genotype TT and TC in the observation group was higher than the control group (P<0.05). Binary logistic regression analysis showed that MTHFR gene TC/CC genotype serum Hcy overexpression may be influencing factor which induced coronary heart disease in patients with hematological diseases (OR=2.107/OR=1.634, P<0.05). ROC curves showed that the AUC of serum Hcy level of MTHFR gene TC/CC genotype and hematological disease complicated with coronary heart disease were both > 0.8. When MTHFR gene TC reaching the optimal threshold of 22.165 μmol/L, the sensitivity was 0.950 and the specificity was 0.837, While MTHFR gene CC reached the optimal threshold of 19.630 μmol/L, the sensitivity was 0.938 and the specificity was 0.826, the best predictive value could be obtained.@*CONCLUSION@#The changes of serum Hcy and MTHFR gene polymorphisms may be involved in the pathological process in patients with hematological diseases complicated with coronary heart disease. In the future, early detection of serum Hcy levels and MTHFR gene polymorphisms in patients with hematological diseases can be used to predict the risk of coronary heart disease.

Research progress of in vitro-in vivo correlation of injectable polylactide-polyglycolide microspheres / 药学学报

As a depot drug delivery system, injectable polylactide-polyglycolide (PLGA) sustained-release microspheres have been successfully used to treat many diseases since the first microsphere product Lupron depot was approved for marketing in the United States in 1989. It has the ability of long-term release in the body for several days to several months, which can not only reduce the times of administration, but also reduce the drug blood concentration fluctuations, significantly improve the safety and patient compliance. In vitro-in vivo correlation (IVIVC) makes the development of microspheres more possible. It can describe the dynamic information of drug release in vivo through the in vitro release behavior of microspheres, and can reduce the workload of each stage and shorten the time span while characterizing the performance of microspheres. IVIVC can provide guidance or support for drug development, production changes, supervision and management. This article summarizes the release mechanism of injectable PLGA sustained-release microspheres, common measurement methods and theories of in vitro and in vivo release. And we also focus on the establishment and application of IVIVC, especially A level IVIVC in the field of microsphere preparations, to provide a reference for further study on in vitro-in vivo correlation of microspheres.

Quality Evaluation System of Standard Decoction of Puerariae Thomsonii Radix / 中国实验方剂学杂志

Objective: To establish the quality control methods for the standard decoction of Puerariae Thomsonii Radix.Method:According to the preparation principles for traditional Chinese medicine (TCM) standard decoction,13 batches of Puerariae Thomsonii Radix from different origins were analyzed under the chromatography conditions established in this study and verified with methodology.By referring to Chinese Pharmacopoeia of 2015,puerarin was used as a quantitative indicator to calculate the transfer rate.In this study,the structures of main chromatographic peaks were also identified to clarify the main chemical constituents in the standard decoction.Result:The 13 batches of medicinal herbs were identified as Puerariae Thomsonii Radix,with a recovery rate of 98.0%,and RSD of 1.1%,indicating that the method was accurate and reliable.The transfer rate ranged from 41.4% to 60.0%,and the extraction rate was within the range of 15.7%-34.3%.The corresponding fingerprints were prepared for 13 batches of the standard decoction,and their similarities were all greater than 90.0%.The chemical constituents from Puerariae Thomsonii Radix were identified by mass spectrometry analysis,including citric acid,4'-O-glucosyl puerarin/daidzein-4',7-diglucoside,3'-hydroxy puerarin/genistein puerarin,puerarin apioside,daidzin puerossid A and daidzein,etc.Conclusion: The 13 batches of Puerariae Thomsonii Radix decoction in different origins had consistent properties with the basic properties of medicinal decoction pieces.The established method of quality evaluation can be used to systematically evaluate the standard decoction,providing reference for quality control of related decoction preparations of Puerariae Thomsonii Radix.

Clinical effect of artificial semi-shoulder joint replacement in treatment of humeral head necrosis / 局解手术学杂志

Objective To explore the clinical effect of the semi-shoulder arthroplasty in the treatment of humeral head necrosis.Methods Twenty patients with head necrosis of the humerus in first hospital affiliated to army medical university from February 2008 to January2018 were collected, including 8 cases of males, 12 cases of females, 7 cases of left shoulder and 13 cases of right shoulder.The patients were aged from 45 to 83 years old, mean (67.40±5.06) years old.All patients were followed up for at least 6 months, the anterior flexion angle, abduction angle, external rotation angle and internal rotation angle of shoulder joint were measured, the function of shoulder joint was evaluated by ASES, UCLA, SST, and VAS, and the imaging examination was conducted.Results All patients were followed up for 6 to 37 months after surgery, with average (18.50±5.31) months, 2 patients presented mild pain during shoulder joint activity, 1 patient presented brachial plexus nerve damage, but returned to normal 3 months after surgery.No complication happened.X-ray reexamination showed good position and angle of the prosthesis during the follow-up period.The preoperative anteflexion angle, angle of outreach, swing angle and swing angle of the shoulder joint were respectively (55.24±8.21) °, (42.58±6.21) °, (12.95±2.74) °, (17.79±3.65) °, the last follow-up were respectively (120.76±13.15) °, (103.08±10.54) °, (33.51±3.14) °, (50.10±7.25) °, the differences were significant (P＜0.01);The preoperative ASES score, UCLA score, SST score, VAS score of the shoulder joint were respectively (38.24±5.21), (12.58±3.93), (3.25±1.42), (6.79±1.65), the last follow-up were respectively (75.74±9.69), (33.08±4.5), (9.11±1.85), (1.45±0.24), the differences were significant (P＜0.01).Conclusion Artificial semi-shoulder replacement for the treatment of humeral head necrosis can significantly improve the range of limb function, relieve the pain symptoms of patients and improve patients'quality of life, which has excellent and good shoulder function rate and fewer complications.

Establishment of a chronic rhinosinusitis model in C57BL/6J mice / 医学研究生学报

Objective Streptococcus pneumoniae is one of the main pathogenic factors of chronic rhinosinusitis (CRS). This study was to explore the method of establishing a CRS model in C57BL/6J mice.Methods Thirty C57BL/6J mice were equally randomized into a CRS model, a sham operation and a blank control group. The CRS model was made by implanting type-Ⅲ streptococcus pneumoniae in the maxillary sinuses, the mice of the sham operation group underwent opening and suturing of the maxillary sinuses without implantation of any streptococcus pneumonia, while the blank controls did not receive any operation. Two months later, all the mice were sacrificed and the nasal sinus mucosal tissue was harvested, embedded with paraffin, sectioned, and subjected to HE staining, followed by observation of the pathological changes under the microscope.Results The CRS model mice exhibited significant proliferation and disorderly arrangement of epithelial cells in the nasal mucosal tissue, with degeneration, necrosis, exfoliation, ulceration, goblet cell proliferation, gland and tissue hyperplasia, and infiltration of lymphocytes, plasmocytes and monocytes. No obvious inflammation was observed in the sham operation and blank control groups. The pathology index score of the nasal sinus mucosal tissue was significantly higher in the CRS model than in the sham operation and blank control groups (\[14.800±5.200\] vs \[2.000±2.906\] and \[1.800±2.098\], P0.05).Conclusion The CRS model was successfully established in mice, which has provided some reference for the construction of the CRS model in animals.

Analysis of KRT9 gene mutation in Chinese Han population / 上海交通大学学报（医学版）

Objective • To explore the main mutation types and pathogenicity of the coding region of keratin 9 gene (KRT9) in Chinese Han population, and to provide reference information for the classification and prediction of clinical diagnosis of the disease with epidermolytic palmoplantar keratoderma (EPPK). Methods • 834 subjects were recruited from 278 families that were not affected by EPPK in the Chinese Han population. The mutations in the coding region of KRT9 gene were detected by using the next-generation sequencing (NGS)-based gene panel combined with Sanger sequencing. The pathogenicity analysis of variants was performed by using SIFT and Polyphen-2 prediction software. Results • A total of twelve KRT9 gene mutations were detected in the Chinese Han population based on 834 individuals from 278 families. Among the twelve different mutations, six synonymous mutations and six missense mutations were identified, respectively. The assessment of pathogenicity of KRT9 gene variants was analyzed by bioinformatics tools, such as SIFT and Polyphen-2 prediction, conservative analysis, and database query. Furthermore, these missense mutations were classified as benign or possibly benign variants. Conclusion • In this study, six missense mutations in the coding region of KRT9 gene exon were detected in the Chinese Han population. According to the American Society of Medical Genetics and Genomics (ACMG) variant classification guide, all the six variants were benign or possibly benign. However, previous reports have found that a KRT9 c.1216T>C (p.C406R) mutation was pathogenic in a pedigree with EPPK, which were inconsistent with our findings, and the pathogenicity of this mutation still has to be verified by further functional experiments.

Distribution and antimicrobial resistance of Acinetobacter baumannii in a geriatric hospital from 2013 to 2016 / 中国感染控制杂志

Objective To analyze the clinical distribution and antimicrobial resistance change trend of Acinetobacter baumannii(AB) from a geriatric hospital in 2013-2016.Methods Specimen source,department distribution,and antimicrobial resistance of AB isolated from all patients in the hospital from 2013 to 2016 were analyzed retrospectively.Results From 2013 to 2016,1 712 strains of AB were isolated,AB isolation rates in 2013,2014,2015,and 2016 decreased year by year,which were 17.92％,17.17％,15.10％,and 11.81％,respectively.AB were mainly isolated from sputum (n =1 524,89.02％),followed by urine (n =79,4.61％) and blood (n=37,2.16％).The main departments of AB isolation were intensive care unit (n =798,46.61％),department of respiratory medicine (n =507,29.62％),and neurology department (n =156,9.11％).Resistance rates of AB to most antimicrobial agents increased in 2013-2016,resistance rates to compound sulfamethoxazole were low (25.68 ％-65.89 ％),followed by resistance rates to cefoperazone/sulbactam (54.74％-68.00％),resistance rates to imipenem were 71.40％-77.42％,to the other antimicrobial agents were all＞60％;in 2013-2016,resistance rates of AB to cefepime,cefoperazone/sulbactam,gentamicin,tobramycin,and compound sulfamethoxazole were significantly different (all P＜0.05).Conclusion Antimicrobial resistance rates of AB in this hospital is increasing,it is necessary to strengthen the monitoring,promote the rational use of antimicrobial agents,and block the infection and transmission of AB in hospital.

Design of CT-guided puncture positioning device / 医疗卫生装备

Objective To design a CT-guided puncture positioning device to shorten puncture time while increase the accuracy. Methods The device realized 3D positioning by the principle of plane geometry, which was composed of a positioner,a fixation mechanism and a direction guiding mechanism for puncture needle.The positioner and direction guiding mechanism were made of transparent plastic, and the fixation mechanism was made of elastic cloth. Results The device gained advantages over the traditional means in puncture time,times of needle insertion and times of CT scanning,and had the puncture success rate in one time being 90%. Conclusion The device behaves well in focal positioning and puncture needle guiding,and thus decreases the probability of failed puncture and the patient pains.

Effects of Rhodiola sachalinensis on ocular blood flow in diabetic retinopathy rats / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of Rhodiola sachalinensis on ocular blood flow in diabetic retinopathy rats. METHODS:A total of 90 SD rats were randomly divided into control group (n=30), model group (n= 30) and intervention group (n=30). Rats in the model group and intervention group were fed with high glucose and high fat diet and injected with streptozotocin (40mg/kg) in order to construct DR model rats,while rats in the control group were fed with basic diet and injected with the same amount of normal saline. After 4wk, the rats in the intervention group were injected with Rhodiola sachalinensis injection(10mL,one per day),while rats in the control group and the model group were injected with normal saline. The course of intervention treatment was 4wk. The ocular blood flow in rats was detected by laser doppler flowmetry, the apoptosis of retinal cells in rats was detected by TUNEL method, the expression of vascular endothelial growth factor (VEGF), glial fibrillary acidic protein ( GFAP ) and glutamate/aspartate transporter (GLAST) in retina of rats was detected by RT-PCR method and Western blot method. RESULTS:The whole blood viscosity,whole blood high shear viscosity,low shear blood viscosity and erythrocyte sedimentation of rats in the model group and intervention group were higher than those in the control group (P<0 01),while the indexes of intervention group were lower than that of model group (P<0.01). The PSV and EDC of rats in the model group and intervention group were lower than those in the control group (P<0.01), and the Rl was higher than that in control group (P<0.01). The PSV and EDC in the intervention group were higher than those in the model group (P<0.01), and Rl was lower than that in the model group (P<0.01). The apoptosis rate of retinal cells of model group and intervention group was higher than that of the control group (P<0.01), that in the intervention group was lower than that in the model group (P<0.01). The expression of VEGF and GFAP in retina tissue of model group and intervention group was higher than that of the control group (P<0.01), and the expression of GLAST was lower than that in the control group(P<0 01). The expression of VEGF and GFAP in the intervention group was lower than that in the model group(P<0.01),and the expression of GLAST was higher than that in the model group (P<0.01). CONCLUSION: Rhodiola sachalinensis injection can significantly improve the ocular blood flow in diabetic retinopathy rats, reduce the apoptosis of retinal cells in rats, down regulate the expression of VEGF and GFAP, and up regulate the expression of GLAST.

Dynamic Change of Red Cell Distribution Width Levels in Prediction of Hospital Mortality in Chinese Elderly Patients with Septic Shock / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The normal range of red cell distribution width (RDW) level is <15%. Several studies have indicated that a high RDW level was associated with mortality in critically ill patients, and the patients with a high RDW level need increased focus in clinical practice. In view of the difficulty in defining the specific value of high RDW level, the key is to focus on the patient with the level beyond the normal upper limit. This study aimed to determine whether dynamic change of RDW levels, rather than the level itself, is predictive of death in elderly patients with septic shock when RDW level is beyond 15%.</p><p><b>METHODS</b>Between September 2013 and September 2015, the elderly septic shock patients with RDW level beyond 15% were enrolled in this study. The RDW levels were measured at enrollment (day 1), and days 4 and 7 after enrollment. Sequential Organ Failure Assessment (SOFA) scores were recorded simultaneously.</p><p><b>RESULTS</b>A total of 45 patients, including 32 males and 13 females, were included in the final analysis. Based on their hospital outcomes, these patients were divided into the survivor group (n = 26) and the nonsurvivor group (n = 19). There were no significant differences in age, gender, body mass index, initial level of RDW, Acute Physiology and Chronic Health Evaluation II scores, and SOFA scores between survivors and nonsurvivors. At days 4 and 7 measurement, both RDW level (median [interquartile range]: day 4: 15.8 [2.0]% vs. 16.7 [2.0]%, P= 0.011; and day 7: 15.6 [1.8]% vs. 17.7 [2.5]%, P= 0.001) and SOFA scores (day 4: 7.0 [4.0] vs. 16.0 [5.0], P< 0.001, day 7: 5.5 [4.0] vs. 17.0 [5.0], P< 0.001) were significantly lower in survivors than those in nonsurvivors. Dynamic changes of RDW and SOFA scores in survivor group were significantly different from those in nonsurvivor group (all P< 0.05). Continuous increase in RDW level was observed in 10 of the 13 nonsurvivors, but only in 3 of the 26 survivors. The level of RDW7 and dynamic changes significantly correlated with their counterparts of SOFA scores (all P< 0.05), whereas the levels of RDW1 and RDW4 had no significant correlation with their counterparts of SOFA scores (all P> 0.05).</p><p><b>CONCLUSIONS</b>Continuous increase in RDW level, rather than the level of RDW itself, was more useful in predicting hospital death in elderly patients with septic shock when the level of RDW was >15%. The dynamic changes of RDW were highly correlated with the SOFA score in the patients.</p>

Study of heterologous efficient synthesis of cucurbitadienol / 中国中药杂志

Cucurbitadienol has anti-inflammation, anti-cancer activities, and acts as a precursor of traditional Chinese medicine active ingredients mogroside and cucurbitacine. For construction of a Sacchromyces cerevisiae cell factory for production of cucurbitadienol, we firstly cloned a cucurbitadienol synthase (CBS) gene from Siraitia grosvenorii. Then, through heterologous expression of CBS in the triterpenoid chassis strain WD-2091, the engineered strain could produced 27.44 mg•L ⁻¹ cucurbitadienol, which was determined by GC-MS. Further regulation of CBS expression led to cucurbitadienol's titer increasing by 202.07% and reaching 82.89 mg•L ⁻¹ in the shake flask fermentation and 1 724.10 mg•L ⁻¹ in the high cell density fermentation. Our research promotes the cucurbitane-type tetracyclic triterpenoids synthesis pathway analysis progress and provides the basis for further obtaining cell factories for production of cucurbitadienol tetracyclic triterpenoids.

Establishment of Double Antibody Sandwich ELISA for the Determination of Human Soluble VE-Cadherin in Human Plasma and Its Application / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To establish double antibody sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of human soluble VE-cadherin in human plasma and to investigate its value in clinical use.</p><p><b>METHODS</b>The monoclonal antibodies against human VE-cadherin were prepared from BALB/c mice immunized with prokaryotic expression recombinant proteins, and the best combination of double antibodies was selected by checkerboard titration method. Double antibody sandwich ELISA for the determination of human VE-cadherin was established by using HRP-labeled McAb as a detection antibody and a capture antibody. The methodology performance was evaluated. The plasma concentrations of VE-cadherin in 28 healthy subjects and 60 patients with cancer were determined.</p><p><b>RESULTS</b>The double antibody sandwich ELISA for the determination of human VE-cadherin was established by selecting the combination of double antibodies. The detection limit was 24.7 pg/ml, the coefficients of variation for inner-batch and inter-batch were 4.1%-7.7% and 8.7%-10.8% respectively. The average recovery was 96.7%. The plasma level of soluble VE-cadherin in normal controls was 262.1±11.75 pg/ml. The plasma level of soluble VE-cadherin was 173.9±17.98 pg/ml in 24 patients with leukemia, 311.7±25.24 pg/ml in 14 patients with stomach cancer, 206.8±25.01 pg/ml in 11 patients with lung cancer, and 310.7±11.82 pg/ml in others patients(9 patients with breast cancer, 1 patients with gliomas, 1 patients with liver cancer).</p><p><b>CONCLUSION</b>The developed ELISA kit has better sensitivity and specificity, and can be used in detection of human soluble VE-cadherin in human plasma, therefore, it can provide a new mathod for diagnosis of cancer patients.</p>

Inhibitory effect of combination of tanshinoneⅠ,metformin and aspirin on malignant melanoma model mice / 中国药理学与毒理学杂志

OBJECTIVE To explore the antitumor effects of combined tanshinoneⅠ(TanⅠ),metformin (Met) and aspirin (Asp) on malignant melanoma in mice and the possible mechanisms. METHODS C57BL/6 mice were injected with 0.1 mL B16F10 cells(2.8×109L-1)to establish the subcutaneous trans-plantation tumor model at the right forelimbs axillary.Then,the mice were divided into 8 groups according to body mass,including model group, TanⅠgroup(20 mg·kg-1,ip),Asp group(210 mg·kg-1,orally in drinking water), Met group (70 mg·kg-1, orally in drinking water), Asp+Met group, TanⅠ+Asp group, TanⅠ+Met group and TanⅠ+Asp+Met group,10 mice in each group.Each mouse drank about 7 mL of water every day for a total of 18 d.The mouse body mass was measured every other day and the tumor diameter was calculated every day. The mice were sacrificed after treatment, the tumor mass was measured and the tumor inhibitory rates were counted. The histopathological changes of the liver and spleen were observed with HE staining. The percentage of lymphocytes in the tumor tissue such as CD8+T,CD4+T and Treg cells was detected by flow cytometry.Inflammatory factors such as interleukin-6 (IL-6),IL-1β and tumor necrosis factor-α (TNF-α) were detected by ELISA. RESULTS The body mass (including tumor mass)of mice in different groups increased during the experiment,but that of TanⅠ+Asp+Met group increased more slower than in model group(P<0.01).At the end of the experiment,no lesions were seen in any liver or spleen tissue by pathological observation,and the number of survivors was 8/10(model group),8/10(TanⅠgroup),7/10(Asp group),7/10(Met group),8/10(TanⅠ+Asp group), 8/10 (TanⅠ+Met group), 7/10 (Asp+Met group) and 5/10 (TanⅠ+Asp+ Met group), respectively. Compared with model group,there were no obvious changes in tumor volume or tumor mass in TanⅠ, Asp and Met groups and other two-two joint groups,but the tumor volume and tumor mass in TanⅠ+Asp+ Met group were significantly decreased (P<0.01, P<0.05), and the tumor inhibitory rate in this group was 46.2%.Compared with the model group,the percentage of CD8+T cells increased(P<0.05) in TanⅠ+Asp+Met group,but there were no significant changes in other groups.The contents of IL-6, IL-1β and TNF-α in tumor tissue of TanⅠ+Met group were much higher than in model group(P<0.01, P<0.05,P<0.05)and the content of IL-6 increased in TanⅠ+Asp+Met group(P<0.01).CONCLUSION Combination of TanⅠ,Asp and Met can effectively inhibit the growth of melanoma in mice,which may be related to the increasing percentage of CD8+T lymphocytes and IL-6 in tumor tissue.However there are possibly some side effects.

Imageology and significances of rotational axes of distal femur on Chinese adults with total knee arthroplasty / 中国骨伤

<p><b>OBJECTIVE</b>To explore clinical significance of rotational axis of distal femur on Chinese adults in total knee arthroplasty (TKA).</p><p><b>METHODS</b>There were 86 Chinese adults (106 normal knees) including 47 males (53 knees) and 39 females (53 knees), 54 knees were on left and 52 on right. The CT scan was employed in the distal femur. The scan direction was aligned to be on the plane perpendicular to the mechanical axis of the femoral. The CT images of cross sections across lateral and medial femoral epicondyle were moved to personal computer,lateral angle between anterior posterior line (APL) and surgical transepicondylar axis (STEA) (ATA),lateral angle between posterior condylar line (PCL) and APL (APA), angle between perpendicularity of APL and PCL (A-PA), posterior condylar angle (PCA), condylar twist angle (CTA), angle between clinical transepicondylar axis (CTEA) and STEA (CSA) were measured. These values were divided into different groups according to gender and side, the values of CTA, PCA, A-PA, angle PT (varus of tibia plateau), constant 3, ATA, APA and constant 90° were compared by statistically. A-PA and PCA, and CTA were analysed statistically with the liner regression, the relationship among CTEA, STEA ,PCL, APL and PLP were performed to assess by liner regression.</p><p><b>RESULTS</b>ATA was (89.79 ± 1.22)°, APA was (84.84 ± 1.83)°, A-PA was (5.16 ± 1.83)°, PCA was (4.80 ± 1.23)°, CTA was (8.23 ± 1.40), CSA was (3.45 ± 0.68)°. All the parameters had no differences on sex and side,but CSA had difference on male and female. There was no difference among angle PT, PCA, A-PA. There was significant difference in CAT, constant 30 and angle PT, PCA,A-PA. There was no difference between ATA and constant 90°, but there was difference between APA and constant 90°. There was relativity between PCA and CTA, and also PCA and A-PA, CTA and A-PA. There was significant relativity between STEA and CTEA, between STEA and APL, between STEA and PCL, and also between APLP, APL and PCL, but there was no significant relativity between PCL and CTEA.</p><p><b>CONCLUSION</b>TKA for Chinese, the section of femoral posterior condyle should be external 5° to obtain the optimum rotational orientation. The property is different entirely between STEA and CTEA, the rotational alignment is not performed according to parallel to the CTEA in distal femur. Among STEA, APL, PCL, the STEA is the most reliable mark ofrotational alignment of the distal femur, and the PCL is the less reliable mark.</p>

Antibody-drug conjugates:design and clinical progress / 药学学报

Antibody-drug conjugates, constructed with monoclonal antibodies, linker and cytotoxins, have distinctive advantages over chemotherapy drugs and antibody drugs in cancer therapy. In this review, the strategy of developing ADCs, and the important progress in past decade are well summarized. The representative ADCs in the pipeline are introduced and characterized with their new features. While, perspective for future directions of ADCs is proposed.

Protection mechanism of deacetylase inhibitor on spleen of rats with severe hemorrhagic shock

OBJECTIVE@#To explore the protection and molecular mechanism of histone deacetylase inhibitors (HDACIs) on the spleen of rats with hemorrhagic shock.@*METHODS@#A total of 60 SPF male SD rats were selected for the modeling of severe hemorrhagic shock using the method of arterial and venous cannulation with the time-divided bleeding. The measurement of mean arterial blood pressure and blood lactic acid was used to verify the modeling. The modeled rats were randomly divided into shock group, shock + suberoylanilide hydroxamic acid (SAHA) group, shock + autogenous transfusion group and shock + SAHA + autogenous transfusion group. Three hours after the treatment, the spleen of rats was collected and TUNEL method was employed to detect the apoptosis of spleen cells in each group. The statistical analysis was performed. Afterwards, real-time PCR and western blot were employed to detect the expression of BCL-2, BAX and caspass3 in the spleen of rats in each group.@*RESULTS@#A total of 53 rats had successful modeling of severe hemorrhagic shock, with success rate of 88%. Cell apoptosis in the severe hemorrhagic model group was the most serious. After the intervention of HDACIs and the autogenous transfusion, the tissue injury was a bit recovered. Cell apoptosis was least in the shock + SAHA + autogenous transfusion group (P < 0.05). After the intervention of HDACIs and the autogenous transfusion, the relative expression of BCL-2 was significantly increased (P < 0.05), with highest relative expression of BCL-2 in shock + SAHA + autogenous transfusion group (P < 0.05). After the intervention of HDACIs and the autogenous transfusion, the relative expression of BAX was significantly decreased (P < 0.05), with lowest relative expression of BAX in the intervention group of single HDACIs. The change in the expression of caspass3 was similar to BAX, namely the relative expression of caspass3 was significantly decreased after the intervention of HDACIs and the autogenous transfusion (P < 0.05).@*CONCLUSIONS@#HDACIs and autogenous transfusion can all protect the spleen injury because of the severe hemorrhagic shock. Its molecular mechanism may be related to the regulation on the expression of BCL-2/BAX and caspass3, which may affect the apoptosis process of cells.

Protection mechanism of deacetylase inhibitor on spleen of rats with severe hemorrhagic shock

Objective To explore the protection and molecular mechanism of histone deacetylase inhibitors (HDACIs) on the spleen of rats with hemorrhagic shock. Methods A total of 60 SPF male SD rats were selected for the modeling of severe hemorrhagic shock using the method of arterial and venous cannulation with the time-divided bleeding. The measurement of mean arterial blood pressure and blood lactic acid was used to verify the modeling. The modeled rats were randomly divided into shock group, shock + suberoylanilide hydroxamic acid (SAHA) group, shock + autogenous transfusion group and shock + SAHA + autogenous transfusion group. Three hours after the treatment, the spleen of rats was collected and TUNEL method was employed to detect the apoptosis of spleen cells in each group. The statistical analysis was performed. Afterwards, real-time PCR and western blot were employed to detect the expression of BCL-2, BAX and caspass3 in the spleen of rats in each group. Results A total of 53 rats had successful modeling of severe hemorrhagic shock, with success rate of 88%. Cell apoptosis in the severe hemorrhagic model group was the most serious. After the intervention of HDACIs and the autogenous transfusion, the tissue injury was a bit recovered. Cell apoptosis was least in the shock + SAHA + autogenous transfusion group (P < 0.05). After the intervention of HDACIs and the autogenous transfusion, the relative expression of BCL-2 was significantly increased (P < 0.05), with highest relative expression of BCL-2 in shock + SAHA + autogenous transfusion group (P < 0.05). After the intervention of HDACIs and the autogenous transfusion, the relative expression of BAX was significantly decreased (P < 0.05), with lowest relative expression of BAX in the intervention group of single HDACIs. The change in the expression of caspass3 was similar to BAX, namely the relative expression of caspass3 was significantly decreased after the intervention of HDACIs and the autogenous transfusion (P < 0.05). Conclusions HDACIs and autogenous transfusion can all protect the spleen injury because of the severe hemorrhagic shock. Its molecular mechanism may be related to the regulation on the expression of BCL-2/BAX and caspass3, which may affect the apoptosis process of cells.

Inhibitory effect of flavonoids from Glycyrrhiza uralensis on expressions of TGF-β1 and Caspase-3 in thioacetamide-induced hepatic fibrosis in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the inhibitory effect of flavonoids from Glycyrrhiza uralensis on thioacetamide-induced chonic hepatic fibrosis in rats and the effect on the protein expressions of transforming growth factor-β1 (TGF-β1) and Caspase-3 in livers.</p><p><b>METHOD</b>Male Sprague-Dawley rats were randomly divided into totally seven groups: the normal control group, the model group, LF groups s (400, 200, 100, 50 mg · kg(-1) · d(-1)) and the silymarin positive control group (30 mg · kg(-1) · d(-1)). The hepatic fibrosis model was induced in the rats through intraperitoneal injection with 3% thioacetamide (TAA) at a dose of 150 mg · kg(-1) body weight twice a week for 12 weeks. During the course, the control group and the model group were orally administered with saline (1 mL · kg(-1) · d(-1)). After the modeling and drug intervention, the pathologic changes and fibrosis in liver tissues were observed by HE staining and Masson's Trichrome staining. The serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and liver hydroxyproline (HYP) contents were assayed by biochemical process. The serum hyaluronic acid (HA) was assessed by radioimmunoassay. In addition, the protein expressions of liver TGF-β1 and Caspase-3 were examined by immunohistochemical method. The mRNA expression of TGF-β1 in hepatic tissues was examined by quantitative Real-time PCR analysis.</p><p><b>RESULT</b>Compared with the model group, flavonoids can protect the integrity of the structure of liver tissues, significantly reduce the hepatic cell degeneration and necrosis and the proliferation of fibrous tissues, notably reduce the serum AST, ALT, ALP and HA and HYP in hepatic tissues and down-regulate the protein expressions of liver TGF-β1 and Caspase-3 and the mRNA expression of TGF-β1 in hepatic tissues.</p><p><b>CONCLUSION</b>The licorice flavonoids can resist the thioacetamide-induced hepatic fibrosis in rats. Its mechanism may be related to the down-regulation of the protein expressions of TGF-β1 and Caspase-3.</p>