[Quality control strategy of traditional Chinese medicine based on pharmaceutical product lifecycle management].

Quality control is pivotal in the research and development of traditional Chinese medicine, whose connotation is not limi-ted to the qualitative or quantitative detection of an indicator component, but extends to the establishment of a whole process quality control system from the perspective of pharmaceutical product lifecycle management. This study discussed the quality control strategy of Chinese medicine based on the concept of pharmaceutical product lifecycle management, and proposed the following suggestions:(1) to focus on the "holistic view" and "phased" characteristics of quality control and strengthen the establishment of quality control strategy based on top-level design;(2) to strengthen the research on quality control of Chinese medicine based on quality risk management, focus on the correlations of quality control indicators with the safety and effectiveness of traditional Chinese medicine, and establish a quality evaluation system consistent with the characteristics of traditional Chinese medicine;(3) to consider the characteristics of different registration classifications in the establishment of quality control strategy;(4) to highlight the quality correlation research, strengthen the quality transfer research, ensure the quality traceability, and establish a sound quality management system;(5) to strengthen the quality research on marketed drugs to achieve dynamic quality improvement.

Reconstruction of the gastric cancer microenvironment after neoadjuvant chemotherapy by longitudinal single-cell sequencing.

BACKGROUND: Little is known on the tumor microenvironment (TME) response after neoadjuvant chemotherapy (NACT) in gastric cancer on the molecular level. METHODS: Here, we profiled 33,589 cell transcriptomes in 14 samples from 11 gastric cancer patients (4 pre-treatment samples, 4 post-treatment samples and 3 pre-post pairs) using single-cell RNA sequencing (scRNA-seq) to generate the cell atlas. The ligand-receptor-based intercellular communication networks of the single cells were also characterized before and after NACT. RESULTS: Compered to pre-treatment samples, CD4+ T cells (P = 0.018) and CD8+ T cells (P = 0.010) of post-treatment samples were significantly decreased, while endothelial cells and fibroblasts were increased (P = 0.034 and P = 0.005, respectively). No significant difference observed with respect to CD4+ Tregs cells, cycling T cells, B cells, plasma cells, macrophages, monocytes, dendritic cells, and mast cells (P > 0.05). In the unsupervised nonnegative matrix factorization (NMF) analysis, we revealed that there were three transcriptional programs (NMF1, NMF2 and NMF3) shared among these samples. Compared to pre-treatment samples, signature score of NMF1 was significantly downregulated after treatment (P = 0.009), while the NMF2 signature was significantly upregulated after treatment (P = 0.013). The downregulated NMF1 and upregulated NMF2 signatures were both associated with improved overall survival outcomes based on The Cancer Genome Atlas (TCGA) database. Additionally, proangiogenic pathways were activated in tumor and endothelial cells after treatment, indicating that NACT triggers vascular remodeling by cancer cells together with stromal cells. CONCLUSIONS: In conclusion, our study provided transcriptional profiles of TME between pre-treatment and post-treatment for in-depth understanding on the mechanisms of NACT in gastric cancer and empowering the development of potential optimized therapy procedures and novel drugs.

Design and Control of a Series-Parallel Elastic Actuator for a Weight-Bearing Exoskeleton Robot.

Weight-bearing exoskeletons are robots that need to carry loads and interact with humans frequently. Therefore, the actuators of these exoskeletons are supposed to be capable of outputting sufficient force with high compliance and little weight. A series-parallel elastic actuator (SPEA) is designed, in this work, to meet the demanding requirements of an exoskeleton robot called PALExo. A gas spring is installed in parallel with an electric cylinder to adjust the force output range of the actuator according to the needs of the exoskeleton. A series elastic module (SEM) is installed in series with the electric cylinder and gas spring to improve the compliance of the actuator, the stiffness of which is variable to adapt to the different stiffness requirements of the exoskeleton's legs in the standing phase and swinging phase. A force controller combining dynamic compensation and a cascade control with an inner velocity loop and a disturbance observer is designed for the SPEA. The performance of the force controller is verified by experiments and the results demonstrate that the controller has good adaptability to the stiffness of the SEM.

Modular Robotic Limbs for Astronaut Activities Assistance.

In order to meet the assist requirements of extravehicular activity (EVA) for astronauts, such as moving outside the international space station (ISS) or performing on-orbit tasks by a single astronaut, this paper proposes an astronaut robotic limbs system (AstroLimbs) for extravehicular activities assistance. This system has two robotic limbs that can be fixed on the backpack of the astronaut. Each limb is composed of several basic module units with identical structure and function, which makes it modularized and reconfigurable. The robotic limbs can work as extra arms of the astronaut to assist them outside the space station cabin. In this paper, the robotic limbs are designed and developed. The reinforcement learning method is introduced to achieve autonomous motion planning capacity for the robot, which makes the robot intelligent enough to assist the astronaut in unstructured environment. In the meantime, the movement of the robot is also planned to make it move smoothly. The structure scene of the ISS for extravehicular activities is modeled in a simulation environment, which verified the effectiveness of the proposed method.

Tripping Avoidance Lower Extremity Exoskeleton Based on Virtual Potential Field for Elderly People.

Tripping is a common problem that everyone faces when walking. This paper mainly focuses on a lower limb exoskeleton that can help those weak in joints to avoid tripping when negotiating stairs or stepping over obstacles. This method does not need a camera or map reconstruction to recognize the obstacles and plan paths. The exoskeleton applies an impedance controller to follow and control the pilot's movements. A virtual potential field is proposed to help the robot regulate the pilot's motion and avoid kicking the obstacles appearing in front of the pilot's foot during walking. Simulation and experiments show that this method works effectively and could help the elderly and those affected by joint weakness avoid tripping when walking.

[Studies of pattern recognition of fingerprint profile of cattle bile powder and determination of multi-component in it].

An HPLC-ELSD method with good specificity and good accuracy was used for the studies of fingerprint and quantification of multi-components for cattle bile powder. The chromatographic analysis was carried out on a Phenomenex Gemini C18 column (4.6 mm×250 mm, 5 µm) with a column temperature of 40 ℃ and a liquid flow-rate of 1.0 mL•min⁻¹ using 10 mmol ammonium acetate solution and acetonitrile as the mobile phase with a linear gradient. An ELSD was used with a nitrogen flow-rate of 2.8 L•h⁻¹, at a drift tube temperature of 110 ℃. The average contents of glycocholic acid, glycodeoxycholic acid, taurocholic acid, taurodeoxycholic acid were (25.2±17.0)%, (4.1±3.4)%, (24.5±20.0)% and (5.2±3.8)% respectively, and the total content of the four bile acids was (59.0±26.0)%. Beyond that, the preprocessing and pattern recognition analysis of the chromatographic fingerprints of samples were applied with chemometric method. The results of this chemometric analysis indicated that the samples from market and self-made samples were different signally, and four regions were noteworthy due to their great impact with poor chromatographic signal. All in one, because this HPLC-ELSD method was simple and accurate, it was suitable for the quality assessment and quality control of cattle bile powder and could be the technological base for its standard perfection.

A Mouth and Tongue Interactive Device to Control Wearable Robotic Limbs in Tasks where Human Limbs Are Occupied.

The Wearable Robotic Limb (WRL) is a type of robotic arm worn on the human body, aiming to enhance the wearer's operational capabilities. However, proposing additional methods to control and perceive the WRL when human limbs are heavily occupied with primary tasks presents a challenge. Existing interactive methods, such as voice, gaze, and electromyography (EMG), have limitations in control precision and convenience. To address this, we have developed an interactive device that utilizes the mouth and tongue. This device is lightweight and compact, allowing wearers to achieve continuous motion and contact force control of the WRL. By using a tongue controller and mouth gas pressure sensor, wearers can control the WRL while also receiving sensitive contact feedback through changes in mouth pressure. To facilitate bidirectional interaction between the wearer and the WRL, we have devised an algorithm that divides WRL control into motion and force-position hybrid modes. In order to evaluate the performance of the device, we conducted an experiment with ten participants tasked with completing a pin-hole assembly task with the assistance of the WRL system. The results show that the device enables continuous control of the position and contact force of the WRL, with users perceiving feedback through mouth airflow resistance. However, the experiment also revealed some shortcomings of the device, including user fatigue and its impact on breathing. After experimental investigation, it was observed that fatigue levels can decrease with training. Experimental studies have revealed that fatigue levels can decrease with training. Furthermore, the limitations of the device have shown potential for improvement through structural enhancements. Overall, our mouth and tongue interactive device shows promising potential in controlling the WRL during tasks where human limbs are occupied.

Reinforcement learning based variable damping control of wearable robotic limbs for maintaining astronaut pose during extravehicular activity.

As astronauts perform on-orbit servicing of extravehicular activity (EVA) without the help of the space station's robotic arms, it will be rather difficult and labor-consuming to maintain the appropriate position in case of impact. In order to solve this problem, we propose the development of a wearable robotic limb system for astronaut assistance and a variable damping control method for maintaining the astronaut's position. The requirements of the astronaut's impact-resisting ability during EVA were analyzed, including the capabilities of deviation resistance, fast return, oscillation resistance, and accurate return. To meet these needs, the system of the astronaut with robotic limbs was modeled and simplified. In combination with this simplified model and a reinforcement learning algorithm, a variable damping controller for the end of the robotic limb was obtained, which can regulate the dynamic performance of the robot end to resist oscillation after impact. A weightless simulation environment for the astronaut with robotic limbs was constructed. The simulation results demonstrate that the proposed method can meet the recommended requirements for maintaining an astronaut's position during EVA. No matter how the damping coefficient was set, the fixed damping control method failed to meet all four requirements at the same time. In comparison to the fixed damping control method, the variable damping controller proposed in this paper fully satisfied all the impact-resisting requirements by itself. It could prevent excessive deviation from the original position and was able to achieve a fast return to the starting point. The maximum deviation displacement was reduced by 39.3% and the recovery time was cut by 17.7%. Besides, it also had the ability to prevent reciprocating oscillation and return to the original position accurately.

Human Operation Augmentation through Wearable Robotic Limb Integrated with Mixed Reality Device.

Mixed reality technology can give humans an intuitive visual experience, and combined with the multi-source information of the human body, it can provide a comfortable human-robot interaction experience. This paper applies a mixed reality device (Hololens2) to provide interactive communication between the wearer and the wearable robotic limb (supernumerary robotic limb, SRL). Hololens2 can obtain human body information, including eye gaze, hand gestures, voice input, etc. It can also provide feedback information to the wearer through augmented reality and audio output, which is the communication bridge needed in human-robot interaction. Implementing a wearable robotic arm integrated with HoloLens2 is proposed to augment the wearer's capabilities. Taking two typical practical tasks of cable installation and electrical connector soldering in aircraft manufacturing as examples, the task models and interaction scheme are designed. Finally, human augmentation is evaluated in terms of task completion time statistics.

Ground Contact Force and Moment Estimation for Human-Exoskeleton Systems Using Dynamic Decoupled Coordinate System and Minimum Energy Hypothesis.

Estimating the contact forces and moments (CFMs) between exoskeletons' feet and the ground is a prerequisite for calculating exoskeletons' joint moments. However, comfortable, portable, and high-precision force sensors for CFM detection are difficult to design and manufacture. In addition, there are many unknown CFM components (six force components and six moment components in the double-support phase). These reasons make it challenging to estimate CFMs precisely. In this paper, we propose a novel method for estimating these CFMs based on a proposed dynamic decoupled coordinate system (DDCS) and the minimum energy hypothesis. By decomposing these CFMs into a DDCS, the number of unknowns can be significantly reduced from twelve to two. Meanwhile, the minimum energy hypothesis provides a relatively reliable target for optimizing the remaining two unknown variables. We verify the accuracy of this method using a public data set about human walking. The validation shows that the proposed method is capable of estimating CFMs. This study provides a practical way to estimate the CFMs under the soles, which contributes to reducing the research and development costs of exoskeletons by avoiding the need for expensive plantar sensors. The sensor-free approach also reduces the dependence on high-precision, portable, and comfortable CFM detection sensors, which are usually difficult to design.

Identification of a 3-Gene Model as Prognostic Biomarker in Patients With Gastric Cancer.

Objective: Although the incidence of gastric cancer (GC) is decreasing, GC remains one of the leading cancers in the world. Surgical resection, radiotherapy, chemotherapy, and neoadjuvant therapy have advanced, but patients still face the risk of recurrence and poor prognosis. This study provides new insights for assessment of prognosis and postoperative recurrence of GC patients. Methods: We collected paired cancer and adjacent tissues of 17 patients with early primary GC for bulk transcriptome sequencing. By comparing the transcriptome information of cancer and adjacent cancer, 321 differentially expressed genes (DEGs) were identified. These DEGs were further screened and analyzed with the GC cohort of TCGA to establish a 3-gene prognostic model (PLCL1, PLOD2 and ABCA6). At the same time, the predictive ability of this risk model is validated in multiple public data sets. Besides, the differences in immune cells proportion between the high- and low-risk groups were analyzed by the CIBERSORT algorithm with the Leukocyte signature matrix (LM22) gene signature to reveal the role of the immune microenvironment in the occurrence and development of GC. Results: The model could divide GC samples from TCGA cohorts into two groups with significant differences in overall and disease-free survival. The excellent predictive ability of this model was also validated in multiple other public data sets. The proportion of these immune cells such as resting mast cells, T cells CD4+ memory activated and Macrophages M2 are significantly different between high and low risk group. Conclusion: These three genes used to build the models were validated as biomarkers for predicting tumor recurrence and survival. They may have potential significance for the treatment and diagnosis of patients in the future, and may also promote the development of targeted drugs.

Differentiation of Various Snake Bile Derived from Different Genus by High-Performance Thin-Layer Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry.

Background: Snake bile originates from nearly 20 species from three families (Elapidae, Colubridae, and Viperidae). However, the components of various snake bile were not compared with one another. Objecive: The aim of the study was to develop a TLC-MS method for differentiation of various snake bile derived from a different genus. Method: As a type of traditional identification method for Chinese herbs, TLC has considerable advantages as a multicomponent separation system. Results: In this paper, TLC was used to separate the components in snake bile. It was found that the snake bile from Colubridae family and Cobra species is different from the others using TLC. The molecular formulas of the bands were elucidated with TLC coupled with quadrupole-time-of-flight-MS by the TLC-MS interface. Two bands on the plate were identified with the reference substance, and the other three bands were analyzed by the TLC-MS method without the reference substance. The corresponding molecular formulas of these bands were given according to accurate molecular weights. Conclusions: The results from this study indicate that the proposed method is reliable, and it has been successfully applied to the identification of snake bile samples.

Analysis of the fingerprint profile of bioactive constituents of traditional Chinese medicinal materials derived from animal bile using the HPLC-ELSD and chemometric methods: An application of a reference scaleplate.

Traditional Chinese medicinal materials derived from animal bile are widely applied in clinical therapy for thousands of years in several Southeast Asian countries. Although the constituents are similar, these crude drugs exhibit different pharmacological activities; bile acids are the main bioactive constituent. Depending on the source, the price of these crude drugs differs significantly. Therefore, a reliable fingerprint method is needed to analyze and distinguish these crude drugs with a similar composition. In this milieu, we aimed to establish a fingerprint chromatography method that can separate and detect several bile acids simultaneously. A high-performance liquid chromatography separation method was established with evaporative light scattering detection to detect the analytes. The main bioactive constituents of pig bile, cattle bile, sheep bile, bear bile, and three types of cow bezoar were analyzed using the proposed method. The fingerprint chromatography profile of 35 samples were obtained and analyzed using chemometric methods. Considering the differences among samples, a reference scaleplate method was used in the peak alignment procedure. Unsupervised methods (hierarchical cluster analysis and principle component analysis) and supervised methods (K-nearest neighbor, partial least squares discriminant analysis, support vector machine discriminant analysis, and soft independent modeling of class analogy) were used in the chemometric analysis. The results indicated that the fingerprint chromatograms of the seven crude drugs had fingerprint specificity and that they can be well distinguished. In addition, the reference scaleplate method using the chromatogram of a mixed standard solution is practically applicable for peak alignment in the analysis of samples with a large difference in chromatographic peaks. Overall, 17 bile acids can be separated and detected simultaneously using this method and some frequently used TCMMs derived from animal bile can be distinguished accurately.

Double closed-loop cascade control for lower limb exoskeleton with elastic actuation.

Unlike traditional rigid actuators, the significant features of Series Elastic Actuator (SEA) are stable torque control, lower output impedance, impact resistance and energy storage. Recently, SEA has been applied in many exoskeletons. In such applications, a key issue is how to realize the human-exoskeleton movement coordination. In this paper, double closed-loop cascade control for lower limb exoskeleton with SEA is proposed. This control method consists of inner SEA torque loop and outer contact force loop. Utilizing the SEA torque control with a motor velocity loop, actuation performances of SEA are analyzed. An integrated exoskeleton control system is designed, in which joint angles are calculated by internal encoders and resolvers and contact forces are gathered by external pressure sensors. The double closed-loop cascade control model is established based on the feedback signals of internal and external sensor. Movement experiments are accomplished in our prototype of lower limb exoskeleton. Preliminary results indicate the exoskeleton movements with pilot can be realized stably by utilizing this double closed-loop cascade control method. Feasibility of the SEA in our exoskeleton robot and effectiveness of the control method are verified.