Advances of targeted protein degradation technology and its applications in diseases therapy / 生物工程学报

Targeted protein degradation (TPD) technology facilitates specific and efficient degradation of disease-related proteins through hijacking the two major protein degradation systems in mammalian cells: ubiquitin-proteasome system and lysosome pathway. Compared with traditional small molecule-inhibitors, TPD-based drugs exhibit the characteristics of a broader target spectrum. Compared with techniques interfere with protein expression on the gene and mRNA level, TPD-based drugs are target-specific, efficaciously rapid, and not constrained by post-translational modification of proteins. In the past 20 years, various TPD-based technologies have been developed. Most excitingly, two TPD-based therapeutic drugs have been approved by FDA for phase Ⅰ clinical trials in 2019. Despite of the early stage characteristics and various obstructions of the TPD technology, it could serve as a powerful tool for the development of novel drugs. This review summarizes the advances of different degradation systems based on TPD technologies and their applications in disease therapy. Moreover, the advantages and challenges of various technologies were discussed systematically, with the aim to provide theoretical guidance for further application of TPD technologies in scientific research and drug development.

Advances in immortalization of human B cells / 生物工程学报

With the advantages of low immunogenicity and long half-life, human monoclonal antibody has become an indispensable biological agent in vivo. Immortalization of human B cells is a potential and effective method to obtain natural human antibody library, which can provide a rich source for the preparation of human monoclonal antibodies. As there are urgent problems to be solved in each platform, the preparation of antibodies based on human B cell immortalization is still limited to the laboratory research stage. At present, there is a lack of a systematic review to clarify the advantages and disadvantages of the existing human B cell immortalization antibody preparation platform and its feasibility analysis. This paper reviews the research on the preparation of human monoclonal antibody based on human B cells immortalization, and describes an in vitro cell culture method, in which hCD40L vesicles are used instead of feeder cells, in order to provide references for the further development of human monoclonal antibody preparation technology.

Laboratory diagnostics within a modular hospital at the time of Coronavirus disease 2019 (COVID-19) in Wuhan.

An outbreak of the so-called Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), has been spreading rapidly nationwide in China since December 2019. Wuhan, Hubei Province, is the hardest-hit region, with a rise in confirmed cases and its hospitals overwhelmed. On 2nd February, 2020, Wuhan began to build a modular hospital to treat patients caught with mild illness. The mobile modular hospital is mainly composed of medical modules, technical support modules, ward units, living support units and transportation capacity under field conditions, and there are complete equipment and specialized personnel to treat patients. Due to the severity and particularity of SARS-CoV-2, taking granted from lessons learnt from mobile modular hospitals, we use the existing large venues to construct a new fixed modular hospital. As patients need to be treated and tested, it is important to develop a clinical laboratory in the modular hospital and ensure biosafety. The construction of a clinical laboratory in the modular hospital is faced with problems such as time pressure, limited site selection, high level of biosafety, lack of experience and so forth. This paper mainly discusses how to construct the clinical laboratory in the modular hospital quickly and safely and put it into use to provide testing service for patients under various limited conditions.

Can the descending aortic stroke volume be estimated by transesophageal descending aortic photoplethysmography?

PURPOSE: The aim of this study was to investigate the ability of transesophageal photoplethysmography detected from the descending aorta (dPPG) for predicting low descending aortic stroke volume (dSV) level in cardiac surgical patients. METHODS: Fifteen patients scheduled for elective cardiac surgery were enrolled in our study. A transesophageal echocardiography (TEE) probe with an attached oximetry sensor was placed into the esophagus for paired dPPG signal and descending aortic Doppler blood flow signal acquisition. Metrics, including alternating current (AC), direct current (DC), area under the curve (AUC) and width (W), were extracted from the dPPG signals. The TEE-measured dSV, which was defined as the blood flow through the descending aorta during a cardiac cycle, was chosen as the standard reference. A receiver operating characteristic (ROC) curve was built to evaluate the performance of dPPG metrics in predicting low dSV level, and dSV measuring agreement between TEE and dPPG was analyzed by the Bland-Altman method. RESULTS: A total of 644 paired dPPG and Doppler signals of the descending aorta were acquired. Significant correlations were found between the dPPG metrics and TEE-measured dSV, and the correlation coefficients between TEE-measured dSV and AUC or AC were 0.64 and 0.66, respectively. AUC and AC values obviously decreased with the reduction of dSV level among the three groups (<20 mL, from 20-40 mL, and >40 mL). The areas under the ROC curve for AUC and AC in predicting low dSV level (<20 mL) were 0.85 and 0.88, respectively. Bland-Altman plot showed a small bias (0.02 mL) but a wide limit of agreement (-18.62 to 18.66 mL) in dSV measurement between dPPG and Doppler technology. CONCLUSIONS: The AC and AUC extracted from the dPPG signal provided a sensitive and qualitative prediction for dSV level. The dSV value could not be accurately measured by dPPG metrics. TRIAL REGISTRATION: Chinese Clinical Trials Register Identifier: ChiCTR-OCS-12002789.

The relationship between hyperuricemia with neutrophil-to-lymphocyte ratio and insulin resistance in type ;2 diabetes mellitus / 实用医学杂志

Objective To research the relationship between Serum uric acid (SUA) levels and the Neu-trophil-to-lymphocyte Ratio (NLR) of Type 2 Diabetes Mellitus (T2DM) patients. Method 273 newly diag-nosed T2DM patients are selected in accordance with the WHO diagnostic criteria: Male subjects with SUA lev-els ≥ 416 μmol/L(70 mg/L), and female subjects with SUA levels ≥ 357 μmol/L (60 mg/L) are sorted into the high SUA (HUA) group (224 subjects), and the rest into the normal SUA (NUA) group (49 subjects). 100 subjects were selected as a control group. One-Way analysis of variance was applied to the data of the three groups; Pearson correlation analysis was used to calculate the correlation of SUA levels , NLR and IR; risk fac-tors influencing SUA levels were analyzed with Logistic regression analysis; ROC curve analysis was used to de-termine the diagnostic value of NLR to HUA, and the optimal threshold value of NLR. Result (1) The NLR and IR of the HUA group was significantly higher than those of the NUA group (2.54 ± 0.63 vs. 2.05 ± 0.61, P < 0.001; 3.70 ± 1.86 vs. 2.71 ± 1.43, P < 0.001); (2) In the HUA group, UA was positively correlated with NLR and IR (respectively r = 0.480, P < 0.001; r = 0.332, P < 0.001). (3)NLR (P < 0.001, EXP(B)= 8.045, 95%CI = 4.597 ~ 14.079) was a risk factor of Hyperuricemia. Conclusion Our results suggest that NLR may be an independent risk factor of Hyperuricemia.

Assessment of postoperative pain intensity by using photoplethysmography.

PURPOSE: Timely assessment of acute postoperative pain is very important for pain management. No objective and reliable method to assess postoperative pain intensity exists till now. The aim of the study was to investigate the feasibility of photoplethysmography (PPG) signals in postoperative pain assessment. METHODS: Thirty patients scheduled for elective abdominal surgery under general anesthesia were examined. Finger PPG signals and visual analogue scale (VAS) score were acquired before and 5, 10, 20, and 30 min after sufentanil administration when the patients were awake and transferred to the post-anesthesia care unit (PACU). During each pain rating, the patient's blood pressure, heart rate, and pulse oxygen saturation were recorded. The amplitude of alternating current (AC) and direct current (DC) extracted from finger PPG signals were analyzed, and the ratio of AC and DC (AC/DC) was calculated. Receiver operating characteristic (ROC) curves were built to assess the performance of AC and AC/DC to detect patients with VAS >4 in the PACU. RESULTS: After administration of sufentanil, VAS scores decreased significantly (p < 0.05), as did blood pressure and heart rate. Simultaneously, both values of AC and AC/DC increased significantly. The VAS score had significant correlations with AC (r = -0.477; p < 0.01), AC/DC (r = -0.738; p < 0.01) and heart rate (r = 0.280; p < 0.01). In contrast, no statistical correlations between VAS score and blood pressure were found. Further analysis found significant differences in both AC and AC/DC among different pain levels, but no obvious differences in blood pressures and heart rate. The area under the ROC curves were 0.754 for AC and 0.795 for AC/DC, respectively. CONCLUSION: The finger PPG signal can be used in acute postoperative pain assessment. Both AC/DC and AC had significant correlations with the pain rating levels, while blood pressure and heart rate were unreliable in pain assessment.

Correlation study of blood uric acid level and carotid atherosclerosis in perimenopausal women / 中国医师进修杂志

[Objective]To observe the relationship between blood uric acid(UA)level and carotid atherosclerosis(CAS)in perimenopausal women.[Methods] Two hundred and thirty-three perimenopausal women were selected.Intima media thickness(IMT)of bilateral carotid arteries were measured by colour Doppler ultrasound.They were divided into normal group(162 cases)and CAS group(71 cases)according to the results of colour Doppler ultrasound.The level of blood UA between two groups was compared and the influence factors of CAS we re analyzed.[Results] The level of blood UA in CAS group was significantly higher than that in normal group[(341 ± 86)μ mol/L vs.(293±78)μ mol/L](P ＜ 0.05).The detection rate of hyperuricemia in normal group was 10.49％(17/162),while the detection rate in CAS group was 40.85％(29/71),which had statistical significance between two groupe(P＜0.01).Pearson correlation analysis showed that CAS had positive correlation with age(r=0.233,P=0.028),body mass index(BMI)(r=0.215,P=0.044),bloodUA(r=0.249,P=0.019)and fasting plasma ghcose(r=0.214,P=0.046).AndCASwas negatively correlated with high density lipoprotein cholesterol(r=-0.224,P=0.036).Logistic regression analysis showed that after the factors of age and BMI were corrected,CAS still had significantly positive correlation with the level of blood UA(OR＝4.805,95％ CI 1.700-11.673,P ＜ 0.05).[Conclusion]Hyperuricemia is a related risk factor of the incidence of carotid atherosclerosis in perimenopausal women.

The source and influential factors in signals of trans-esophageal oxygen saturation / 生物医学工程学杂志

This paper is aimed to investigate the signal source and influential factors in signals of trans-esophageal pulse oxygen saturation (SeO2). The red light of the SeO2 probe was faced directly to the descending aorta (DA) of the mongrel dogs. The readings and waveform of SeO2 signals were recorded under following conditions: before and after DA was shield; before and after the blood supply of esophagus was cut off; under the different touch pressures between the SeO2 probe and the esophageal wall. The readings and waveform of SeO2 signals were also recorded respectively at both different esophageal depth and directions when mechanical ventilation was on and off. The tongue oxygen saturation (StO2) was recorded simultaneously as control. The waveform of SeO2 signals disappeared after DA was shield (P < 0.001). No significant difference was found in the SeO2 signals before and after the blood supply of esophagus was cut off (P > 0.05). Compared with the StO2 readings when the SeO2 probe was placed at different esophageal depth, the waldeyer ring, cervical area and thoracic inlet,the readings of SeOz significantly decreased (P < 0.05) while mechanical ventilation was on and off. However, there was no significant difference in the readings between SeO2 signals from DA, aortic arch (AA) and left subclavian artery and the StO2 signals recorded simultaneously. Mechanical ventilation had a remarkable effect on the SeO2 signals at different esophageal depth (P < 0.05), but the StO2 signals lay in its insensitivity to its influence. The readings of StO2 signals were significantly different from that of StO2 signals when the touch pressure between the SeO2 probe and the esophageal wall below 40 mmHg (P < 0.01). The directions of the optimum SeO2 signals acquired at different esophageal depth were not the same. The SeO2 signals were primarily derived from deeper arteries around the esophagus. All of Mechanical ventilation, location of the SeO2 probe in the esophagus and the touch pressure between the probe and esophageal wall can influence SeO2 signals.