Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.

A complete plant body consists of elements on different scales, including microscopic molecules, mesoscopic multicellular structures, and macroscopic tissues and organs, which are interconnected to form complex biological networks. The growth and development of plants involve the regulation of elements on different scales and their biological networks, which requires the coordinated operation of multiple molecules, cells, tissues, and organs. It is difficult to reveal the essence of multi-level life activities by a single method or technology. In recent years, the development of various novel imaging technologies has provided new approaches for revealing the complex life activities in plants. Using multi-modal imaging technologies to study the cross-scale network connections of plants from the microscopic, mesoscopic, and macroscopic levels is crucial for understanding the complex internal connections behind biological functions. This paper first summarizes multi-modal cross-scale imaging technologies, three-dimensional reconstruction, and image processing methods, outlines the basic framework of cross-scale network connection properties, and then summarizes the applications of multi-modal imaging technologies in elucidating plant multi-scale networks. Finally, this review systematically integrates the combined analysis of cross-scale 3D spatial structural data and single-cell omics, laying a theoretical foundation for the innovation of novel plant imaging technologies. Furthermore, it provides a new research paradigm for in-depth exploration of the interaction mechanisms among cross-scale elements and the principles of biological network connectivity in plant life activities.
Plants/metabolism* ; Imaging, Three-Dimensional/methods* ; Image Processing, Computer-Assisted/methods* ; Multimodal Imaging/methods* ; Plant Physiological Phenomena

With the advancement of synthetic biology, recombinant proteins are poised to play a significant role in medical applications. The scaled manufacturing is a pillar for the extensive application and development of recombinant proteins across various fields. In the large-scale production process of recombinant proteins, the removal and detection of endotoxins are essential to reduce their levels to safe thresholds in the final products. Currently, establishing stringent endotoxin limits for different recombinant protein products is a crucial aspect of safety assessment. This review begins by shedding light on the pathogenicity of endotoxins and discusses the methods for the removal and determination of endotoxins during the production processes of recombinant proteins. Subsequently, this review summarizes the endotoxin limits in industries such as biologics, medical devices, and human recombinant DNA products, particularly those in recombinant protein injection products. It is highlighted that regardless of whether the hosts for recombinant protein expression are bacteria or not, endotoxin testing is required for the final products of injectable recombinant proteins, and compliance with relevant industry standards is necessary. This review aims to provide a reference for the research on endotoxins in the large-scale production process of recombinant proteins.
Endotoxins/genetics* ; Recombinant Proteins/genetics* ; Humans ; Drug Contamination/prevention & control*

Objective:To establish the biology reference interval (RI) of peripheral blood procalcitonin (PCT) for children between 3 days and 6 years old in China.Methods:Totally 3 353 reference individuals with apparent health or no specific diseases were recruited in 18 hospitals throughout the country during October 2020 to May 2021. Reference individuals were divided into four groups: 3-28 days, 29 days - 1 year, 1-3 years and 4-6 years. Vein blood or capillary blood were collected by percutaneous puncture from every reference individual. The PCT level in serum and the capillary whole blood were assayed by Roche Cobas e601 and Norman NRM411-S7 immunoanalyzer. Outliers were deleted and 95th percentiles of every group were provided as RIs. Man-Whitney U test or Kruskal-Wallis test were used performed to assess the difference among different gender, age or method groups. Results:The difference of PCT distribution between male and female is not statistically significant, but the difference between serum and capillary whole blood is statistically significant. The differences between age groups are significant too. For Roche e601, serum PCT RI of 3-28 days group is <0.23 μg/L, 29 days - 6 years are <0.11 μg/L. For NRM411, Serum PCT RI of 3-28 days group is <0.21 μg/L, 29 days - 1 year: <0.09 μg/L, 1 - 6 years: <0.10 μg/L. For whole blood PCT, RI of 3-28 days group is <0.26 μg/L, 29 days - 6 years is <0.15 μg/L.Conclusions:Serum and capillary whole blood PCT have different RIs, however, capillary whole blood PCT testing is valuable in pediatric application. Children in 3-28 days show higher PCT levels than other age group. To establish the RIs and understand the differences among different groups are essential for the interpretation and clinical application of peripheral blood PCT testing results.

The morbidity of scoliosis in adolescents in China is about 3%-5%, 80%-85% of the patients are adolescent idiopathic scoliosis (AIS), whose etiology is unknown. Scoliosis is a structural spine disease occurring during puberty or before skeletal maturation. Scoliosis has a greatly negative impacton not only the growth and development of adolescent spine, but also the mental health of adolescents. Ocular disease is a common clinical disease in which the eye ball and its accessory structures have structural abnormalitiesordys function. Ocular disease snotonly bring in convenience to patients's life, but also may induce diseases in other organs. Recent studies have shown that various ocular diseases may have a potential impact on scoliosis, and quite a fewof patients with certain ocular diseases have higher incidence rate of scoliosis. Therefore, in this article, the etiological relationship between eye diseases and scoliosis will be summarized, which provides guidance and direction for the etiological research of scoliosis and eye diseases. After sorting out, we found that the relationship between ophthalmic diseases and scoliosis mainly concentrated in the following four aspects: choroidal thickness and scoliosis, Goldenhar syndrome, gene level and strabismus. Among them, the genetic relationship is the most complex, about 40 kinds of gene or chromosome abnormalities have been found to cause ocular diseases and scoliosis; Goldenhar syndrome, also known as oculo-auriculo-vertebral spectrum, first revealed the relationship between ocular diseases and scoliosis, but the current statistical relationship is still very vague. There are few studies on choroidal thickness and strabismus at home and abroad, which are statistical studies, only revealing the relationship between choroidal thickness and scoliosis, and there are many defects in the study of choroidal thickness, which need further research.

Objective:To summarize the clinical experience in transoral endoscopic thyroidectomy via sublingual and vestibular approach (TOETSLVA).Methods:We retrospectively reviewed the medical record of patients who underwent TOETSLVA in our department from November 2011 to May 2020, including 3 males and 95 females, aged from 18 to 57 years old. Initial 81 cases were categorized in "Period A (November 2011-November 2015)" and subsequent 17 cases in "Period B (August 2019-May 2020)" . Data about demographics, operation time and complications were collected. SPSS 22.0 software was used for statistical analysis.Results:In Period A, the average age of patients was (34.2±9.4) years old; the mean tumor diameter was (2.33±0.80) cm; postoperative pathology showed benign nodules in 76 cases and malignant carcinoma in 5 cases; there were 65 cases of unilateral subtotal thyroid lobectomy, 6 cases of isthmus lobectomy, and 5 cases of bilateral subtotal thyroid lobectomy, with the mean operation time of (132.70±47.22) min; in 5 cases of unilateral thyroid lobectomy with central lymph node dissection, the mean operation time was (185.4±31.40) min; postoperative neck infections occurred in 6 cases; temporary vocal cord paralysis occurred in 1 case, which it recovered within two months; and CO 2 gas embolism occurred in 2 cases. In Period B, the average age of patients was (35.1±8.5) years old; mean tumor diameter was (1.32±0.67) cm; postoperative pathology indicated malignant nodules in 15 cases and benign nodules in 2 cases; in 2 cases of unilateral thyroid lobectomy, the mean operation time was (153.5±34.64) min; in 15 cases of unilateral thyroid lobectomy with central lymph node dissection, the mean operation time was (123.73±14.26) min; and none of patients developed postoperative neck infections or CO 2 gas embolism. All patients had different degree of cutaneous numbness in the submandibular region after surgery, which recovered within 1-2 weeks. There were no complications such as postoperative secondary hemorrhage, permanent vocal cord paralysis, hypoparathyroidism in both the periods. The median follow-up time was 86 months (57-105 months) in Peroid A and 5 months (3-12 months) in Peroid B. During the follow-up periods, there were no obvious abnormalities in swallowing, chewing, oral sensory function and neck activity, and also no tumor recurrence or metastasis. Conclusions:TOETSLVA is a safe and feasible surgery method, with a good cosmetic result. This approach will not lead to a postoperative cutaneous numbness of the submandibular region for a long time.

Paraneoplastic neurological syndromes (PNS) are a rare group of immune-mediated disorders that affect the central and peripheral neuromuscular system in association with cancer.If the limbal lobe system of the brain is involved,it will show paraneoplastic limbal encephalitis(PLE).The discern of patients with PNS is challenging since tumors causing paraneoplastic neurologic disorders are often asymptomatic and sometimes occult.We report a case of PLE with double positive anti-Hu and Yo antibodies,and further analyze and discuss it in conmbination with relevant literature to improve the understanding of the disease.

Objective To compare the imported (Diasorin,Italy) and domestic (Mindray,Shenzhen) chemiluminescent systems used in the measurement of plasma aldosterone and renin concentrations;To establish the reference interval of plasma aldosterone and renin concentrations in healthy adults.Methods With the assay instrument and its kits from Italy Diasorin as the reference system,the concentrations of plasma aldosterone and renin were measured by the two systems,in 143 healthy adults,72 patients with hypertension (16 patients with primary aldosteronism) and to establish the medical reference range (P2.5-P97.5) of them.Results The plasma aldosterone (r=0.914,P＜0.01) and renin(r=0.977,P＜0.01)concentrations detected by the two systems were positively correlated.Distribution of plasma aldosterone and renin was skewed in healthy adults.The reference interval was 30.8-344.6 pg/ml for aldosterone and 2.4-90.0 μIU/ml for renin by the imported chemiluminescent system.The reference interval was 29.4-473.3 pg/ml for aldosterone and 3.6-98.3 μIU/ml for renin by the domestic chemiluminescent detection system.Conclusion The two systems are closely correlated in measuring plasma aldosterone and renin concentrations.

Objective: To analyze the clinical characteristics and long-term outcomes with multicenter study for acute lymphoblastic leukemia (ALL) in children over 10 years old and adolescents. Method: Newly diagnosed ALL patients aged from 10 to 18 years old in three hospitals were included in the study from May 1^st 2005 to April 30^th 2015. They were received ALL-2005/2009 protocol following up to December 31^st 2016. The clinical characteristics, outcomes and the prognostic analysis were evaluated between the two protocols. Results: Totally, 237 patients were involved in the study, 76 cases for ALL-2005 and 161 cases for ALL-2009 protocol. Complete remission (CR) after induction therapy was 94.5%. 64 (28.6%) patients relapsed with a median time of 14.5 months and 70 (29.5%) patients passed away during the following time. In long-term follow-up, the 5-year event-free survival (EFS) and 5-year overall survival (OS) of ALL patients were (63.1±3.3)% and (68.4±3.2)%. The 7-year EFS and OS were (61.0±3.5)% and (67.6±3.3)%.The 5-year EFS of intermediate risk group in ALL-2005 and ALL-2009 protocol were (73.6±6.1)% and (71.7±4.3)% with no difference (χ²=0.064, P=0.801). The 5-year EFS of high risk group in two protocols were (27.6±9.6)% and (33.9±9.3)%, showing no significant difference (χ²=0.296, P=0.586). Five years relapsed rate of two protocols were (33.8±5.7)% and (32.6±4.1)% with no difference (χ²=0.055, P=0.815). The mortalities were 36.8% and 29.8% separately (χ²=2.869, P=0.090). Univariate analysis indicated that age, male, risk, BCR/ABL translocation/t(9;22) and resistant to induction were risk prognostic factors in long-term survival (χ²=4.764, 4.796, 46.410, 9.560, 25.450; P=0.029, 0.029, <0.001, 0.049, <0.001). Cox multivariate analysis showed male, risk and resistant to induction were independent risk prognostic factors (RR=1.790, 2.727, 2.719; P=0.021, 0.000, 0.012). Conclusion Protocol ALL-2009 enhanced the chemotherapy intensity in intermediate risk group with no benefit of survival. BCR-ABL fusion or t(9;22) translocation was still the risk factor of prognosis. TKI inhibitor used in these patients could improve survival. EFS rate was increased a little and death rate was decreased in ALL-2009 protocol with no significant lower relapsed rate comparing with ALL-2005 protocol.

Objective: To explore the effects of macrophages with high expression of TL1A on the activation and proliferation of HSCs in vitro. Methods: The Bone marrow-derived macrophages (BMMs) and peritoneal macrophages (PMs) from wild type (WT) and myeloid-overexpressed TL1A transgenic mice were isolated, differentiated and activated. HSCs were harvested from activated macrophages culture supernatant (CM). HSCs were detected by immunofluorescence and real-time Q-PCR. And the proliferation was detected by CCK-8 and BrdU assay kit. The levels of IL-1β and PDGF-BB in macrophage culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA). Results: BMMs-derived CM-intervention HSCs were used to detect the expression of α-smooth muscle actin (α-SMA) on the 2nd, 4th and 6th day respectively by immunofluorescence method. There was no significant difference between the two groups on the 2 nd and the 6th day, P > 0.05; On day 4, the CM/Tg group was significantly higher than that of CM/WT group, P < 0.01; the results of CMs derived from PMs were consistent with the above trend. The expression of α-SMA mRNA on the 2nd, 4th and 6th day was detected by real-time Q-PCR method using BM-derived CMs. No significant difference was found between the groups on the 2nd day (P > 0.05).α-SMA mRNA increased further on the 4th and 6th day, and the level of CM/Tg in CM/Tg group was significantly higher than that in CM/WT group (P < 0.05). The detection results of CMs derived from PMs were consistent with the above trend. The results of CCK-8 assay and BrdU assay showed that the proliferation rate of HSCs in CM Tg group was significantly higher than that in CM/WT group (P < 0.01). The CMs derived from PMs were used to interfere with HSCs. And the results were consistent with the above trend. For BMMs, the levels of IL-1β and PDGF-BB in the lipopolysaccharide (LPS) + IFNγ/Tg culture supernatant were significantly higher than those in the LPS+IFNγ/WT group (P < 0.01). For the culture supernatants of PMs Liquid test results consistent with the above trend. Conclusion Macrophages with high expression of TL1A could enhance the activation and proliferation of HSCs by increasing the secretion of IL-1β and PDGF-BB.