Glioma is the most common malignancy of the central nervous system, originating mainly from glial cells. Because of its highly aggressive nature, glioma has one of the highest rates of death among all types of cancer. Therefore, it is very important to develop new therapeutic approaches and drugs for glioma treatment. Instead of activate the telomerase, approximately 30% of glioma use alternative lenthening of telomere (ALT) to maintain telomere length. The mechanism of ALT development is poorly understood, however, some genetic mutations have been reported to induce the development of ALT glioma, such as ATRX, IDH1, p53, etc. The lack of ALT glioma cell lines and preclinical ALT glioma models has limited the mechanistic studies of ALT glioma. Therefore, this review listed ALT glioma cell lines that derived from primary culture or gene editing in the last decade, as well as the xenografted animal models established by ALT glioma cell lines, and discussed the role and significance these cell and animal models play in preclinical studies.

Owing to the advancement in pharmaceutical technology, traditional Chinese medicine industry has seen rapid development. Preferring conventional manufacturing mode, pharmaceutical enterprises of traditional Chinese medicine have no effective process detection tools and process control methods. As a result, the quality of the final products mainly depends on testing and the quality is inconsistent in the same batch. Process analytical technology(PAT) for traditional Chinese medicine manufacturing, as one of the key advanced manufacturing techniques, can break through the bottleneck in quality control of medicine manufacturing, thus improving the production efficiency and product quality and reducing the material and energy consumption. It is applicable to the process control and real-time release of advanced manufacturing modes such as intelligent manufacturing and continuous manufacturing. This paper summarized the general idea of PAT for traditional Chinese medicine manufacturing. Through the analysis of the characteristics and status quo of the technology, we summed up the methodology for the continuous application and improvement of PAT during the whole life-cycle of traditional Chinese medicine. The five key procedures(process understanding, process detection, process modeling, process control, and continuous improvement) were summarized, and the application was reviewed. Finally, we proposed suggestions for the technical and regulatory challenges in implementing PAT in traditional Chinese medicine industry. This paper aims to provide a reference for development and application of PAT in advanced manufacturing, intelligent manufacturing, and continuous manufacturing of traditional Chinese medicine industry.
Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; Technology, Pharmaceutical ; Drug Industry ; Quality Control

The application of new-generation information technologies such as big data, the internet of things(IoT), and cloud computing in the traditional Chinese medicine(TCM)manufacturing industry is gradually deepening, driving the intelligent transformation and upgrading of the TCM industry. At the current stage, there are challenges in understanding the extraction process and its mechanisms in TCM. Online detection technology faces difficulties in making breakthroughs, and data throughout the entire production process is scattered, lacking valuable mining and utilization, which significantly hinders the intelligent upgrading of the TCM industry. Applying data-driven technologies in the process of TCM extraction can enhance the understanding of the extraction process, achieve precise control, and effectively improve the quality of TCM products. This article analyzed the technological bottlenecks in the production process of TCM extraction, summarized commonly used data-driven algorithms in the research and production control of extraction processes, and reviewed the progress in the application of data-driven technologies in the following five aspects: mechanism analysis of the extraction process, process development and optimization, online detection, process control, and production management. This article is expected to provide references for optimizing the extraction process and intelligent production of TCM.
Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; Quality Control ; Big Data ; Algorithms

This study investigated the differences in excretion kinetics of three alkaloids and their four metabolites from Simiao Pills in normal and type 2 diabetic rats. The diabetes model was established in rats by injection of streptozotocin, and the alkaloids in urine, feces, and bile of normal and diabetic rats were detected by LC-MS/MS to explore the effect of diabetes on alkaloid excretion of Simiao Pills. The results showed that 72 h after intragastric administration of the extract of Simiao Pills, feces were the main excretion route of alkaloids from Simiao Pills. The total excretion rates of magnoflorine and berberine in normal rats were 4.87% and 56.54%, which decreased to 2.35% and 35.53% in diabetic rats, which had statistical significance(P<0.05). The total excretion rates of phellodendrine, magnoflorine, and berberine in the urine of diabetic rats decreased significantly, which were 53.57%, 60.84%, and 52.78% of those in normal rats, respectively. After 12 h of intragastric administration, the excretion rate of berberine in the bile of diabetic rats increased significantly, which was 253.33% of that of normal rats. In the condition of diabetes, the excretion rate of berberine metabolite, thalifendine significantly decreased in urine and feces, but significantly increased in bile. The total excretion rates of jateorrhizine and palmatine in the urine increased significantly, and t_(1/2) and K_e changed significantly. The results showed that diabetes affected the in vivo process of alkaloids from Simiao Pills, reducing their excretion in the form of prototype drug, affecting the biotransformation of berberine, and ultimately increasing the exposure of alkaloids in vivo, which would be conducive to the hypoglycemic effect of alkaloids. This study provides references for the clinical application and drug development of Simiao Pills in diabetes.
Rats ; Animals ; Bile/metabolism* ; Chromatography, Liquid/methods* ; Berberine ; Diabetes Mellitus, Experimental/metabolism* ; Chromatography, High Pressure Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Feces ; Alkaloids/metabolism* ; Diabetes Mellitus, Type 2/metabolism*

Objective: To investigate the wearing of masks and the knowledge of masks among high-risk positions for overseas import and pollution transmission. Methods: From May 14 to 17, 2022, a convenient sampling method was used to conduct an online survey among 963 workers in high-risk positions for overseas import and pollution transmission in Beijing. The behaviors of individual use and wearing masks, the distribution and supervision of the unit, the knowledge of personal mask protection and the subjective feelings of wearing masks were analyzed. The χ(2) test and logistic regression model were used to analyze the influencing factors of the correct selection of masks. Results: The majority of the workers in high-risk positions for overseas import and pollution transmission were male (86.0%, 828/963), age concentration in 18-44 years old (68.2%, 657/963), and the majority of them had college or bachelor degrees (49.4%, 476/963). 79.4%(765/963) of the workers chose the right type of masks, female, 45-59 years old and high school education or above were the risk factors for correct selection of masks (P <0.05). Workers had good behaviors such as wearing/removing masks, but only 10.5% (101/963) could correctly rank the protective effect of different masks. 98.4% (948/963) of the workers believed that their work units had provided masks to their employees, and 99.1% (954/963) and 98.2%(946/963) of them had organized training and supervision on the use of masks, respectively. 47.4%(456/963) of the workers were uncomfortable while wearing masks. Conclusion: The overall selection and use of masks among occupational groups in high-risk positions for overseas import and pollution transmission in China need to be further standardized. It is necessary to strengthen supervision and inspection on the use of masks among occupational groups, and take improvement measures to improve the comfort of wearing masks.
Humans ; Male ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Cross-Sectional Studies ; Masks ; China ; Surveys and Questionnaires ; Beijing

Background Ultrasound-guided continuous thoracic paravertebral block can provide pain-relieving and opioid-sparing effects in patients receiving open hepatectomy. We hypothesize that these effects may improve the quality of recovery (QoR) after open hepatectomy. Methods Seventy-six patients undergoing open hepatectomy were randomized to receive a continuous thoracic paravertebral block with ropivacaine (CTPVB group) or normal saline (control group). All patients received patient-controlled intravenous analgesia with morphine postoperatively for 48 hours. The primary outcome was the global Chinese 15-item Quality of Recovery score on postoperative day 7, which was statistically analyzed using Student's t-test. Results Thirty-six patients in the CTPVB group and 37 in the control group completed the study. Compared to the control group, the CTPVB group had significantly increased global Chinese 15-item Quality of Recovery scores (133.14 ± 12.97 vs. 122.62 ± 14.89, P = 0.002) on postoperative day 7. Postoperative pain scores and cumulative morphine consumption were significantly lower for up to 8 and 48 hours (P < 0.05; P = 0.002), respectively, in the CTPVB group. Conclusion Perioperative CTPVB markably promotes patient's QoR after open hepatectomy with a profound analgesic effect in the early postoperative period.
Anesthetics, Local/therapeutic use* ; Double-Blind Method ; Hepatectomy/adverse effects* ; Humans ; Morphine/therapeutic use* ; Pain Measurement ; Pain, Postoperative/etiology* ; Ultrasonography, Interventional

As intelligent production of traditional Chinese medicine （TCM） has been inevitable， informatization and automation of the production process have become the precondition for realizing intelligent manufacturing of TCM， of which the accumulation of critical material attribute and the critical quality attribute are the basis. The study of material properties is of great significance to achieve the quality control of the final product in the process， but there is a lack of systematic induction and summary of the research on the attribute of TCM pills. Therefore， the authors analyzed and summarized the attributes of raw materials， excipients and intermediates in the pill unit process according to the classification of powder properties， rheological properties and texture properties. What’s more， the impact of material attributes on the quality of the final product was summarized. Besides， this review summarized the attribute characterization techniques involved in the pill process and provided some suggestions for the characterization of product quality attributes. Finally， based on the concept of quality by design （QbD）， the authors proposed that the study of material attribute should be combined with process analytical technology （PAT）， and the focus of drug quality control should be moved forward to guide equipment upgrading， so as to realize intelligent continuous manufacturing of TCM pills.

The mixing process is one of the key operation units for solid preparation of traditional Chinese medicine. The physical properties such as particle size, density and viscosity of the mixture are key factors that need to be controlled, which will directly affect the performance of the preparation molding process and product quality. Subsequent dripping process performance and appearance qua-lity of dripping pills will be affected by dynamic viscosity of materials in the mixing process. Based on this, with mixing process of compound Danshen dripping pills as the object, a feedforward control method for the dripping pill mixing process was established based on the concept of quality by design(QbD). Firstly, critical quality attribute(CQA)-dynamic viscosity, critical material attributes(CMAs)-the moisture content of compound Danshen extract, average molecular weight of polyethylene glycol 6000 and critical process parameter(CPP)-mixing temperature were identified through the analysis of properties for multiple batches of the raw materials and excipients as well as technological mechanism. Then the Box-Behnken experimental design was used to establish the regression model among CMA, CPP and CMA(R■=0.972 0, RMSE =16.24) to obtain the design space. Finally, through the verification of three batches within the design space, the mixing process temperature was adjusted according to the properties of the raw materials and exci-pients to achieve accurate control of the dynamic viscosity attribute. The relative deviation between the actual dynamic viscosity value and the target value was less than 3.0 %. The feedforward control of the mixing process of compound Danshen dripping pills was rea-lized in this study, which can contribute to improving quality consistency of the mixing process intermediates, simultaneously provide a reference for the research on the process quality control of other Chinese medicine dripping pills.
Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Quality Control ; Research Design

Objective:To study the effect of Suanzaoren Tang on energy metabolism of liver mitochondria in aged rats with chronic rapid eye movement （REM） sleep deprivation. Method:Fifty male Wistar rats were randomly divided into the control group， model group， estazolam group （0.18 mg·kg^-1·d^-1）， and low- （6.48 g·kg^-1·d^-1） and high-dose （12.96 g·kg^-1·d^-1） Suanzaoren Tang groups. Rats in all groups except for the control group received subcutaneous injection of D-galactose and then were deprived of sleep using the multiple platform method after the last administration. Following successful modeling， the rats in each group were treated with intragastric administration of the corresponding drugs for seven consecutive days. The morphology of liver mitochondria was observed under the transmission electron microscope. The content of adenosine triphosphate （ATP） in rat liver was detected by colorimetry， and the activities of ubiquinone oxidoreductase （complex Ⅰ）， succinate-ubiquinone oxidoreductase （complex Ⅱ）， ubiquinol-cytochrome c oxidoreductase （complex Ⅲ）， and cytochrome c oxidase （complex Ⅳ） in mitochondrial respiratory chain of rat liver were measured by colorimetry. The protein expression levels of citrate synthase （CS）， isocitrate dehydrogenase （IDH）， and ATP synthase， H⁺ transporting， mitochondrial F0 complex， subunit b， isoform 1 （ATP5F1） in rat liver were assayed by Western blot. Result:The mitochondrial damage in rat liver of the model group was more serious than that in the control group， manifested as mitochondrial swelling and deformation as well as cristae rupture and reduction. The comparison with the model group revealed that both the positive control and Suanzaoren Tang at the high dose obviously alleviated the mitochondrial swelling and deformation and reduced cristae rupture， with better improvements observed in the high-dose Suanzaoren Tang group. Compared with the control group， the content of ATP， the activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， and Ⅳ， and the protein expression levels of IDH， CS， and ATP5F1 in rat liver of the model group were all significantly decreased （P<0.01）. Compared with the model group， the content of ATP， the activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， and Ⅳ， and the protein expression levels of IDH， CS， and ATP5F1 in rat liver of the high-dose Suanzaoren Tang group were all significantly increased （P<0.05，P<0.01）. In the positive control group， the content of ATP， the activities of mitochondrial respiratory chain complexes I and Ⅲ， and the protein expression levels of CS and ATP5F1 in rat liver were significantly increased （P<0.05， P<0.01）. The activities of mitochondrial respiratory chain complexes Ⅰ and Ⅲ and the ATP5F1 protein expression in the low-dose Suanzaoren Tang group were significantly elevated （P<0.05， P<0.01）. Conclusion:Suanzaoren Tang alleviates the abnormal liver energy metabolism induced by chronic REM sleep deprivation in the elderly rats， which may be related to its enhancement of mitochondrial electron transport chain enzyme activities and the up-regulation of protein expression levels of CS， IDH and ATP5F1.

Texture analyzer is a multifunctional physical property analyzer. Through a variety of test modes such as compression， puncture， shearing and stretching， hardness， adhesion， elasticity， cohesiveness and other physical property parameters are characterized. The results are objective， sensitive， and accurate， which can provide theoretical basis and reference for interpretation of basic theoretical， optimization of prescription technology and quality control research of pharmaceutical preparations. Firstly， the principles， test modes， measurement indexes and measurement data analysis methods of texture analyzer were summarized in this paper. Secondly， the application progress of texture analyzer in solid preparations， semi-solid preparations， liquid preparations， traditional Chinese medicine decoction pieces and their intermediates was described in detail， and compared with the commonly used measurement methods of physical property indicators. Finally， the application prospects of texture analyzer and its research contents to be improved were reviewed， so as to facilitate the use of texture analyzer by pharmaceutical researchers to promote the development of related fields of pharmaceutics， and to provide new ideas and methods for the research and development of pharmaceutical preparations.