On the Relationship between Doctors and Patients in Court in Qing Dynasty from the Perspective of Famous Doctors’ Diary / 中国医学伦理学

In Qing Dynasty, doctor-patient relationship in the imperial court had distinct characteristics because of the particularity of the objects of diagnosis and treatment. Diaries of famous doctors has become an important research material from a unique perspective. Ji En Lu and Bei Xing Ri Ji contain many research materials on doctor-patient relationship in Qing Palace. By systematically sorting out the contents of the royal doctor-patient relationship in the two diaries, and analyzing them in detail from the three dimensions of doctors, patients and diagnosis and treatment situations, it can be known that patients’ strong performance will interfere with the diagnosis and treatment process to a great extent, and doctors’ low status makes it difficult for them to cope with the complicated diagnosis and treatment environment and affects the curative effect. Learn from the past and the present, further provide reference for the current patient strong special doctor-patient relationship.

Professor ZHANG Boli's Experience in Treating Stubborn Bi （痹） with Ruxiang （Olibanum）-Moyao （Myrrha） Pair / 中医杂志

This paper summarized professor ZHANG Boli's experience in treating stubborn bi （痹） with the herbal pair of Ruxiang （Olibanum）- Moyao （Myrrha）. The basic pathogenesis of stubborn bi is channel and collateral stasis and obstruction. Ruxiang and Moyao are thus used in mutual reinforcement to rectify qi and diffuse bi， activate blood and relieve pain， thereby removing static and obstructed qi and blood， unblocking the obstructed channels and colla-terals， which is especially suitable for stubborn bi caused by channel and collateral obstruction. In clinical practice， the herbal pair of Ruxiang-Moyao is used together with qi-moving and blood-activating medicinals to treat chest bi by expelling stasis and diffusing stagnation， dissipating cold and unblocking vessels. To treat long-term wither and weakness in late stage of stroke， the medicinals of boosting qi and invigorating blood， unblocking channels and venting collaterals can be added to the herbal pair so as to soothe and drain vessels and collaterals， harmonize and regulate qi and blood. Simiao Yongan Decoction （四妙勇安汤） can be integrated in the treatment of vessel bi by moving qi and dissolving stasis， and for the long-term stubborn vessel bi， integrated internal and external treatment is suggested by external use of Ruxiang-Moyao to vent bi with aromatics. Moreover， it is emphasized to use the herbal pair of Ruxiang-Moyao in accordance with indications and cautions.

Correlation between quantitative parameters of dynamic contrast?enhanced MRI after neoadjuvant chemotherapy and pathological grades in esophageal squamous cell carcinoma / 中华放射学杂志

Objective To investigate the correlation between quantitative parameters of dynamic contrast?enhanced MRI (DCE?MRI) after neoadjuvant chemotherapy and pathological grades in esophageal squamous cell carcinoma. Methods Fifty?six patients with esophageal squamous cell carcinoma who were confirmed by esophagoscope and received neoadjuvant chemotherapy before operation between September 2015 and December 2017 in the Affiliated Cancer Hospital of Zhengzhou University were prospectively analyzed, and MRI examination was performed within one week before operation. All patients underwent routine chest MRI and DCE?MRI scanning, and quantitative parameters of DCE?MRI, including volume transfer constant (Ktrans),exchange rate constant (Kep) and extravascular extracellular volume fraction (Ve) were measured. Pathological grading was assessed as highly differentiated, moderately differentiated, poorly differentiated,and undifferentiated. Intraclass correlation coefficient (ICC) was calculated from the results of two radiologists. Kruskal?Wallis H test was used to compare the differences of quantitative parameters between different pathological grade groups of DCE?MRI,and Mann?Whitney U test was utilized to compare the intraclass differences among pathological grades. Spearman rank correlation analysis was performed for evaluating the correlation between DCE?MRI parameters and pathological grade of esophageal squamous cell carcinoma. The receiver operating characteristic (ROC) curves were used to evaluate the diagnosis accuracy of different DCE?MRI parameters in pathological grade of esophageal squamous cell carcinoma after neoadjuvant chemotherapy. Results The 56 patients were divided into four groups according to pathological findings: well differentiated group (n=8), moderately differentiated group (n=39), poorly differentiated group (n=9) and undifferentiated group (n=0). The differences of Ktransmean,Ktrans75%,Kepmax, Kepmean,Kep75% between different pathological grading groups were statistically significant (all P<0.05),and these parameters showed positive correlation significantly with pathological grading (r values were 0.778, 0.632, 0.594, 0.725, 0.489 respectively, all P<0.05). The ROC curve area of Ktransmean, Ktrans75% in the diagnosis of pathological grade for esophageal squamous cell carcinoma was 0.750,0.856,respectively. The diagnostic efficiency of Ktrans75% was the best with the diagnostic threshold of 0.693/min,sensitivity of 87.5%, specificity of 78.5%, respectively. Conclusion The quantitative parameters of DCE?MRI after neoadjuvant chemotherapy in esophageal squamous cell carcinoma have the potential value for predicting pathological grade.

The value of 3 T MR in preoperative T staging of potentially resectable esophageal cancer compared withendoscopicultrasonography / 中华放射学杂志

Objective To evaluate the value of 3T magnetic resonance imaging (MRI) in the preoperative T staging of potentially resectable esophageal cancer(EC), compared with endoscopic ultrasonography (EUS). Methods Patients with resectable EC pathologically confirmed by biopsy from March 2015 to September 2016 were prospectively enrolled. All patients underwent MRI (including T2-TSE-BLADE,DWI and radial-VIBE)and EUS one week after the biopsy,and MRI were performed prior to EUS, both MRI and EUS were acquired within one week before surgery. Two readers with more than 5 years experiences in the MRI diagnosis evaluated the MR image quality using a 5-point score independently. T staging was assigned on MRI and EUS by the two MRI readers using double-blind method and one endoscopist in accordance with the 7th edition of AJCC TNM Classification for EC, and any disagreement between two MRI readers was resolved by consensus with discussion to the third senior MRI doctor. The inter-observer agreement between two MRI readers were calculated using Kappa test for image quality scores and T staging results. Considering postoperative pathological T staging results as the gold standard, the performances of MRI and EUS were evaluated based on the accuracy rate and analyzed by χ2 test. Results A total of 70 patients were enrolled in the study, the good image quality cases (≥ 3 scores) were 66 in reader 1 and 68 in reader 2. The inter-observer agreement of the image quality scores by two readers was excellent (Kappa=0.824, P<0.05). The pathological results revealed 16 cases of T1 stage, 18 cases of T2 stage, 30 cases of T3 stage, and 6 cases of T4a stage. The inter-observer agreement of the preoperative T staging of EC by two readers was excellent (Kappa=0.809, P<0.05). The accuracy rates of MRI and EUS for preoperative T staging of EC were 92.9% (65/70) and 67.1% (47/70), respectively, and the difference in accuracy rates of two techniques was statistically significant (χ2=14.5, P<0.05). Conclusions The accuracy rate of MRI for preoperative T staging of EC is significantly higher than that of EUS. MRI can be used as a noninvasive method for preoperative T staging of EC.

Effect of minimal increase in postsurgical creatinine on prognosis in patients undergoing cardiac surgery with cardiopulmonary bypass / 中华麻醉学杂志

The medical records of patients underwent thoracic surgery with cardiopulmonary bypass (CPB) from July 1,2013 to May 30,2014 were collected and reviewed,the patients who developed postsurgical acute kidney injury (increase in postsurgical serum creatinine＞26.6 μmol/L) during hospital stay were excluded,and a total of 1 509 cases were enrolled in the study.Age,gender,body weight,presurgical complications,presurgical ejection fraction,serum concentration of creatinine on presurgical day 1,CPB duration during surgery,aortic clamping time,volume of blood transfused,duration of intensive care unit stay,mechanical ventilation time,length of hospital stay,and the highest serum concentration of creatinine were collected.The patients were divided into 2 groups according to the increase in postsurgical serum creatinine concentrations (the difference between the highest serum concentration of creatinine during hospital stay and the serum concentration of creatinine on presurgical day 1):no increase in creatinine group (n =508) and minimal increase in creatinine group (increase in postsurgical serum creatinine concentrations≤26.6 μmol/L,n=1 001).All the patients were followed up by telephone,and the fatality was recorded.Kaplan-Meier and log-rank analyses were used to analyze the survival condition,and the risk factors for fatality were identified by using multivariate Cox regression analysis.Compared with no increase in creatinine group,age was significantly increased,the constituent ratios of coronary heart disease,hypertension,diabetes mellitus,and pulmonary hypertension were significantly increased,CPB duration and length of hospital stay were significantly prolonged (P＜0.05),and no significant change was found in the fatality rate on postsurgical day 30 in minimal increase in creatinine group (P＞0.05).The patients were followed up for (298±104) days,and Kaplan-Meier analysis showed that the long-term fatality rate was significantly higher in minimal increase in creatinine group than in no increase in creatinine group (P＜0.05).Multivariate Cox regression analysis showed that age,presurgical coronary heart disease,CPB duration and minimal increase in postsurgical creatinine were the risk factors for fatality,and among these factors,minimal increase in postsurgical creatinine resulted in a 9％ increase in the fatality rate.In conclusion,minimal increase in postsurgical creatinine can not only prolong the length of hospital stay,but also increase the long-term fatality rate in the patients undergoing cardiac surgery with CPB.

The research on protective effect of penehyclidine hydrochloride in rats with myocardial ischemia/reperfusion injury / 中华危重病急救医学

Objective To compare the protective effect of different dose of penehyclidine hydrochloride (PHC) in rats with myocardial ischemia/reperfusion (I/R) injury.Methods Forty-eight healthy male Wistar rats were randomly divided into six groups (n =8 each):sham group,sham + 1.0 mg/kg PHC group (sham + H-PHC group),I/R group,I/R + 0.1 mg/kg PHC preconditioning group (I/R + L-PHC group),I/R + 0.3 mg/kg PHC preconditioning group (I/R + M-PHC group),and I/R + 1.0 mg/kg PHC preconditioning group (I/R + H-PHC group).I/R injury model was reproduced by ligation followed by release of the coronary artery,and PHC in different dosages was given at 30 minutes before model reproduction.At 3 hours after reperfusion,the left ventricular end-diastolic pressure (LVEDP),left ventricular end-systolic pressure (LVESP),ejection fraction (EF),and fractional shortening (FS) were recorded.The levels of aspertate aminotransferase (AST),MB isoenzyme of creatine kinase (CK-MB),and lactate dehydrogenase (LDH) were determined.The myocardial tissues were harvested for the determination of the area at risk (AAR) and the infarct area (AI),and the percentage of AI/AAR was calculated.The examination of myocardial fiber was performed with electron microscopy.Results Compared with sham and sham + H-PHC groups,LVEDP was increased in I/R groups,LVESP,EF and FS were decreased,and the levels of AST,CK-MB and LDH,as well as the AI/AAR were increased.Compared with I/R group,in pretreatment groups with different doses of PHC,LVEDP was decreased,LVESP,EF and FS were increased,the levels of AST,CK-MB,LDH,and AI/AAR were also decreased,especially in I/R+M-PHC and I/R+H-PHC groups [LVEDP (mmHg,I mmHg =0.133 kPa):11.33± 1.17,9.85± 1.09 vs.15.82 ± 1.79,LVESP (mmHg):98.9 ± 10.6,112.8 ± 10.0 vs.87.8 ± 9.2,EF:0.681 ± 0.074,0.741 ± 0.070 vs.0.569 ± 0.072,FS:(42.4 ± 4.6)％,(46.0 ± 5.1)％ vs.(36.8 ± 3.9)％,AST (U/L):386.97 ± 80.65,298.31 ± 54.88 vs.603.47 ± 173.66,CK-MB (U/L):3.12 ± 0.84,2.88 ± 0.72 vs.7.14 ± 1.54,LDH (U/L):1 784.23 ± 488.49,1 629.37 ± 436.34 vs.2 489.14 ± 460.80,AI/AAR:0.284 ± 0.014,0.223 ± 0.008 vs.0.377 ± 0.011,all P ＜ 0.05].There was significant difference in LVEDP,LVESP,and AI/AAR between I/R + M-PHC group and I/R + H-PHC group (all P ＜ 0.05),and no significant difference in other parameters (all P ＞ 0.05).It was showed by electron microscopic examination that after I/R injury,the myocyte mitochondria membranes were broken,mitochondria were markedly swollen,mitochondrial cristae disappeared;however in I/R+M-PHC and I/R+H-PHC groups,mitochondrial swelling was mild,the capsule was more or less intact,mitochondrial cristae were partly visible,the structure was complete,especially in the group I/R+H-PHC,and the mitochondrial structure was close to normal.Conclusions PHC could protect myocardial from I/R injury.Mid dose of PHC (0.3 mg/kg) and high dose of PHC (1.0 mg/kg) could provide better protective effect than low dose of PHC (0.1 mg/kg),and high dose of PHC is better in effect than the middle dose.

Stability analysis of CHO cell line expressing heterologous rhBMP2 / 生物工程学报

Bone morphogenetic protein 2 (BMP2), which belongs to the transforming growth factor-beta (TGF-beta) superfamily, is a multifunctional molecule with distinct abilities to induce bone formation. BMP2 has been identified to have eminent pharmaceutical importance for clinical application. We previously constructed stable cell line in Chinese hamster ovary cells (CHO) that highly expressed recombinant human BMP2 (rhBMP2). For large-scale production of the recombinant protein used in clinical application, it is critical to have both high expression and stability of the protein. In the present study, the stability of the cell line (rCHO(hBMP2)-C8) with the highest expression, as well as the stability of rhBMP2 protein were investigated systematically. We cultured the rCHO (hBMP2)-C8 cell line in the presence or absence of MTX for two months, the cell growth and rhBMP2 production characteristics were examined during the culture; we found the duration that the rCHO(hBMP2)-C8 cell line could secret rhBMP2 continually into the serum-free medium. Moreover, we detected the temperature sensitivity of rhBMP2 in culture medium. This study will contribute to our understanding for further producing rhBMP2 by large-scale culture technology.

Effect of different tags on pulldown assays implemented by LMO2 fusion protein / 生物工程学报

Pulldown assay is an in vitro method for studies of protein-protein interactions, in which tagged proteins are usually expressed as the bait to enrich other proteins that could bind to them. In this technology, the GST tag is broadest used for its modest size and hydrophilic property. In most cases, the GST tag could increase the hydrophility of the fusion protein and help to avoid the formation of inclusion bodies. However, in the other few cases, the target protein may be strongly hydrophobic or have complicated structures that were hard to fold and assemble in correct conformations without champerons, and even the existence of GST tag could not make them soluble. These proteins were always expressed as inclusion bodies and had no functions. LMO2 was a small molecular weight and insoluble protein, in this study, GST system and MBP system were used to express GST-LMO2 and MBP-LMO2 fusion proteins, respectively. We found that GST-LMO2 fusion protein was expressed as inclusion bodies whereas MBP-LMO2 fusion protein was expressed in soluble form. Moreover, the production rate of MBP-LMO2 was also much higher than GST-LMO2. Then MBP-LMO2 fusion proteins and renatured GST-LMO2 fusion proteins were used as bait in pulldown assay to study the interaction between LMO2 and endogenous GATA1 in K562 cells. Western blot analyses showed that both of these proteins could bind to endogenous GATA1 in K562 cells, but recovered GATA1 protein by MBP-LMO2 fusion protein was much more than GST-LMO2 fusion protein. These results suggest that using of MBP system is a helpful attempt in the case of studying small molecular weight, strong hydrophobic proteins.

Establishment and characterization of a mouse medulloblastoma cell line / 基础医学与临床

Objective To study the molecular mechanism of medulloblastoma.Methods The cell line with PARP-1 and P53 null mutation was established and characterized.Mouse medulloblastoma cell line derived from PARP-1/P53 double knockout mice was established.We analyzed cell characters after 30 passages,using neuronal cell-specific markers by immunofluorescence.The cells were transfected with pEGFP-C1-Hparp-1 and pEGFP-C1 plasmids,the expression of PARP-1 protein was detected by immunofluorescence stainning and Western blot.Results The cells showed positive immunoactivity for the neuronal-specific markers such as Vimentin,Dcx and ?Ⅲ-Tubulin,and cells were negative for PARP-1 protein.Exogenous PARP-1 expression was visualized by immunofluorescence and Western blot analysis after pEGFP-C1-Hparp-1 transfection.Conclusion Mouse medulloblastoma cell line with defective function for DNA damage recovery has been successfully established,which provides a useful tool for further dissecting the molecular mechanism and pathogenesis of medulloblastoma.

THE REGULATORY EFFECT OF XENOPUS OOCYTE CYTOPLASM ON THE FUNCTIONAL ACTIVITY OF INJECTED MAMMALIAN NUCLEI / 解剖学报

The present study was designed to investigate the regulatory effect of Xenopus oocyte cytoplasm on the functional activity of the injected mammalian erythroid nuclei taken from different developmental stages and the tumor cell nuclei from human HeLa and mouse plasmocytoma (Sp 2/0) cell lines. Experimental results demonstrated that: (1) only 1/3 of the injected erythroid nuclei derived from different physiological status survived and - were induced to become enlarged, accompanied by chromatin dispersion, clear nucleoplasm, and with the ability of incorporation of~3H-uridine for the synthesis of RNA, while most of the injected nuclei in pyknosis or in late differentiated stage were inactivated, stained black and degenerated steadily; (2) almost all the "injected tumor cell nuclei originally in active division of Sp 2/0 and HeLa survived and were activated by showing nuclei enlarged to about 10 to 200 times with fully chromatin dispersion, concomitant clear nucleoplasm and well developed nuclcoli. The state of activation is much more pronounced than that in erythroid nuclei; (3) isoelectrophoretic analysis of the oocytes with transplanted nuclei showed a dark band at pi 6.28 which is corresponding to a homologous component, but other than hemoglobin from rat bone marrow erythrocytes. It is suggested that the gene activities of the injected nuclei were reprogrammed by the oocyte cytoplasm, globin gene originally activated were closed and oocyte selected to open genes that suitable to host genetic state; (4) when injected into Xenopus oocyte with purified rat globin mRNA polyribosomes, it translated efficiently into hemoglobin. The above mentioned results could be concluded that the Xenopus oocyte provided favorable conditions for the translation of purified mRNA polysomes as well as to regulate or reprogram the expression of gones in the injected nuclei. The regulatory effect is closely related to the initial physiological status and the competence of the injected nuclei themselves responsed to oocyte cytoplasm, i.e. the efficiency is much more prominent in originally active proliferative nuclei than those in late or terminal differentiation.