Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

Aim To express and purify recombinant hCGH-CTP fusion protein in high-density suspension culture of Chinese hamster ovary cells (CHO-S), and to verify the lipid accumulation effect of rhCGH-CTP on 3T3-L1 mature adipocytes. Methods The recombinant protein expression vector (pcDNA3. 1-rhCGH-CTP) was constructed, achieved by fusing the human glycoprotein hormone beta 5/alpha 2 cDNA with CTP Linker. The expression plasmid was transiently transfected into the suspended CHO-S to express rhCGH-CTP protein and then purified, and the protein biological activity was verified. Intervention with 3T3-L1 mature adipocyte cells for 24 h was performed to detect the changes of intracellular triglyceride (TG) level. Results Western blot results showed that rhCGH-CTP protein was successfully expressed in CHO-S cells, and the yield was up to 715. 4 mg • L~ . The secreted protein was purified by AKTA pure system with higher purity that was up to 90% as identified by SDS-PAGE. In addition, the intracellular cAMP content of mature adipocytes with high expression of TSHR gene significantly increased after intervention with different concentrations of rhCGH-CTP protein by ELISA kit, indicating that rhCGH-CTP protein had biological activity. Oil red 0 staining showed that compared with the control group, the lipid content of mature adipocytes in the intervention groups with different concentrations of rhCGH-CTP protein significantly decreased (P < 0. 05) . Conclusions The rhCGH-CTP protein has been successfully expressed and purified with biological activity, and effectively reduce TG. This research provides an important theoretical basis for further revealing the physiological role of CGH protein and its potential application in clinical practice.

Five flavonoid glycosides were isolated from the methanol and ethyl acetate fractions of the ethanol extract of Diphylleia sinensi by using various chromatographic methods, including silica gel, MCI gel, Sephadex LH-20, ODS and semi-preparative HPLC. The structures of the isolated compounds were identified as diphyflavonoid A (1), diphyflavonoid B (2), quercetin-3-O-β-D-glucopyranoside (3), kaempferol-3-O-β-D-glucopyranoside (4), kaempferol-3-O-(6″-O-acetyl)-β-D-glucopyranoside (5) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, and MS). Compounds 1 and 2 were two new flavonoid glycosides, and compounds 3 and 5 were isolated from the genus Diphylleia for the first time.

Sesquiterpenes are natural terpenoids with 15 carbon atoms in the basic skeleton, which mainly exist in plant volatile oil and have important physiological and medicinal value. Cytochrome P450 (CYP450) is a kind of monooxygenase encoded by supergene family, which is one of the largest gene families in plants. It is involved in the synthesis and metabolism of terpenoids, alkaloids and other secondary metabolites. In the process of terpene biosynthesis, CYP450 participates in the post-modification stage of terpenes by introducing functional groups such as hydroxyl, carboxyl and carbonyl, which plays an important role in enriching the diversity of terpenes. The CYP450 enzymes involved in sesquiterpene synthesis and their substrate catalytic specificity mechanisms have been partially investigated. In this paper, the biosynthetic pathway of plant sesquiterpenes, the structure and classification of CYP450 enzymes were briefly introduced, and the CYP450 enzymes involved in sesquiterpene biosynthesis were summarized, in order to provide a reference for intensive study of the role of CYP450 enzymes in the synthesis of sesquiterpenoids.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

The breakthrough progress of implantable brain-computer interfaces (iBCIs) technology in the field of clinical trials has attracted widespread attention from both academia and industry. The development and advancement of this technology have provided new solutions for the rehabilitation of patients with movement disorders. However, challenges from many aspects make it difficult for iBCIs to further implement and transform technologies. This paper illustrates the key challenges restricting the large-scale development of iBCIs from the perspective of system implementation, then discusses the latest clinical application progress in depth, aiming to provide new ideas for researchers. For the system implementation part, we have elaborated the front-end signal collector, signal processing and decoder, then the effector. The most important part of the front-end module is the neural electrode, which can be divided into two types: piercing and attached. These two types of electrodes are newly classified and described. In the signal processing and decoder section, we have discussed the experimental paradigm together with signal processing and decoder for the first time and believed that the experimental paradigm acts as a learning benchmark for decoders that play a pivotal role in iBCIs systems. In addition, the characteristics and roles of the effectors commonly used in iBCIs systems, including cursors and robotic arms, are analyzed in detail. In the clinical progress section, we have divided the latest clinical progress into two categories: functional rehabilitation and functional replacement from the perspective of the application scenarios of iBCIs. Functional rehabilitation and functional replacement are two different types of application, though the boundary between the two is not absolute. To this end, we have first introduced the corresponding clinical trial progress from the three levels: application field, research team, and clinical timeline, and then conducted an in-depth discussion and analysis of their functional boundaries, in order to provide guidance for future research. Finally, this paper mentions that the key technical challenges in the development of iBCIs technology come from multiple aspects. First of all, from the signal acquisition level, high-throughput and highly bio-compatible neural interface designing is essential to ensure long-term stable signal acquisition. The electrode surface modification method and electrode packaging were discussed. Secondly, in terms of decoding performance, real-time, accurate, and robust algorithms have a decisive impact on improving the reliability of iBCIs systems. The third key technology is from the perspective of practicality, we believe that the signal transmission mode of wireless communication is the trend of the future, but it still needs to overcome challenges such as data transmission rate and battery life. Finally, we believe that issues such as ethics, privacy, and security need to be addressed through legal, policy, and technological innovation. In summary, the development of iBCIs technology requires not only the unremitting efforts of scientific researchers, but also the participation and support of policymakers, medical professionals, technology developers, and all sectors of society. Through interdisciplinary collaboration and innovation, iBCIs technology will achieve wider clinical applications in the future and make important contributions to improving the quality of life of patients.

Pharmaceutical cocrystals is an advanced technology to improve the physicochemical and biological properties of drugs. However, there are few studies on the in vivo metabolism of pharmaceutical cocrystals. In this study, the pharmacokinetics of wogonin cocrystal in normal rats was further studied on the basis of the previous preparation of wogonin-aloperine cocrystal. Firstly, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for simultaneous determination of wogonin and its metabolite wogonoside in rat plasma, and to investigate the methodology. The method was applied to the pharmacokinetic study of wogonin-aloperine cocrystal (Wog-Alop) in rats. The results showed that wogonin and its metabolite wogonoside had a good linear relationship in the range of 1-800 ng·mL^-1, and the precision, accuracy, matrix effect and stability in this range met the requirements of biological analysis. Compared with direct administration of wogonin, the C_max of wogonin and its metabolite in rats increased to 7.44-fold and 9.15-fold, AUC_0-t increased to 1.67-fold and 3.72-fold, and oral bioavailability of wogonin increased to 187.66% after cocrystal administration. Wog-Alop cocrystal can significantly improve the C_max, AUC, and oral bioavailability of wogonin and its metabolite, which provides a new perspective for the clinical application of wogonin. This study was approved by the Experimental Animal Ethics Review Committee of Beijing University of Chinese Medicine (approval number: BUCM-2023032307-1148).

The abuse of novel phenylcyclohexylpyridine drugs poses a significant threat to societal safety. The novel psychoactive substance 2-methyl-deschloroketamine (2-MDCK), belonging to the phenylcyclohexylpyridine class, has recently surfaced as a new compound. However, there is a lack of understanding regarding its metabolic pathways and the identification of suitable biomarkers. In this study, a human liver microsomal model was established, and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technology was applied to investigate the in vitro metabolism and products of 2-MDCK. The results indicate that 2-MDCK undergoes various metabolic reactions, including dehydrogenation, deamination, hydroxylation, and demethylation, leading to the formation of eight metabolites. By conducting actual testing on hair samples from 2-MDCK abusers, the existence of six metabolites was confirmed. Comparing the metabolic products in the liver microsomal in vitro model, M3.1 and M4.1 were identified as biomarkers for 2-MDCK consumption. Five samples of abusers of 2-methyl-dechloroketamine were provided by the Anti-Drug Brigade of the Hangzhou Public Security Bureau. Negative hair samples were provided by laboratory volunteers, and all samples were obtained with the informed consent of the volunteers. These findings provide a scientific basis for the detection and identification of 2-MDCK and its metabolites, as well as crucial support for the study of the metabolic mechanisms of similar novel psychoactive substances in the phenylcyclohexylpyridine class. This research holds significant importance in addressing the issue of abuse of new psychoactive substances.

Objective:To describe the epidemiological characteristics and trends of leukemia incidence in Qidong between 1972 and 2021, and provide guidelines for prevention and control measures and strategies.Methods:The cancer registry data was collected and analyzed on leukemia incidence during 1972—2021 in Qidong by sex, age and time. Crude incidence rate (CR), China age-standardized rate (ASRC), world age-standardized rate (ASRW), and average annual change percentage (AAPC) was calculated by Joinpoint software. Age-period-cohort (APC) model was used to analyze the influence of age, period and birth cohort on the changes in the incidence trend of leukemia patients.Results:From 1972 to 2021, there were 2 948 patients with leukemia in Qidong, accounting for 2.00% of all cancer new cases, CR of leukemia was 5.26/10 5, ASRC was 4.34/10 5, ASRW was 4.35/10 5. The truncated incidence of 35—64 years old was 5.29/10 5, the cumulative incidence rate between the ages of 0 and 74 years old was 0.40%, the cumulative risk was 0.40%. There were 1 608 male patients, the CR, ASRC, and the ASRW were 5.81/10 5, 4.88/10 5 and 4.85/10 5. The number of female patients were 1 340, and the CR, ASRC, and the ASRW were 4.71/10 5, 3.86/10 5 and 3.91/10 5, respectively. Temporal trends indicated significant upward trends in ASRC among both gender, males and females with AAPC values of 1.41% ( P＜0.001), 1.15% ( P＜0.001), and 1.73% ( P＜0.001), respectively. The results of the APC model showed that the average net drift value of leukemia incidence in all age groups was 1.57% (95% CI, 1.24%-1.89%), and the highest value of local drift was 3.20% (95% CI, 1.63%-4.78%) in the 80~ years old group. The incidence of leukemia increased with age. With the passage of time, the risk of leukemia incidence increased gradually compared with the rate ratio of leukemia incidence (risk ratio [ RR], 1.00) in 1992—1996, the RR of leukemia incidence increased from 0.70 during 1972—1976 to 1.57 during 2017—2021. The later the cohort was born, the greater the risk of leukemia incidence compared with the relative risk of leukemia incidence ( RR, 1.00) in 1952—1956 cohort, the RR of leukemia incidence increased from 0.24 in the 1892—1896 cohort to 2.73 in the 2017—2021 cohort. Conclusions:The incidence of the leukemia has presented a rising trend in the past fifty years. Leukemia incidence increased with age, and the period and cohort effects on the risk of incidence increase. Further research is needed to investigate the risk factors related to leukemia.

Objective:To describe the epidemiological characteristics and trends of leukemia incidence in Qidong between 1972 and 2021, and provide guidelines for prevention and control measures and strategies.Methods:The cancer registry data was collected and analyzed on leukemia incidence during 1972—2021 in Qidong by sex, age and time. Crude incidence rate (CR), China age-standardized rate (ASRC), world age-standardized rate (ASRW), and average annual change percentage (AAPC) was calculated by Joinpoint software. Age-period-cohort (APC) model was used to analyze the influence of age, period and birth cohort on the changes in the incidence trend of leukemia patients.Results:From 1972 to 2021, there were 2 948 patients with leukemia in Qidong, accounting for 2.00% of all cancer new cases, CR of leukemia was 5.26/10 5, ASRC was 4.34/10 5, ASRW was 4.35/10 5. The truncated incidence of 35—64 years old was 5.29/10 5, the cumulative incidence rate between the ages of 0 and 74 years old was 0.40%, the cumulative risk was 0.40%. There were 1 608 male patients, the CR, ASRC, and the ASRW were 5.81/10 5, 4.88/10 5 and 4.85/10 5. The number of female patients were 1 340, and the CR, ASRC, and the ASRW were 4.71/10 5, 3.86/10 5 and 3.91/10 5, respectively. Temporal trends indicated significant upward trends in ASRC among both gender, males and females with AAPC values of 1.41% ( P＜0.001), 1.15% ( P＜0.001), and 1.73% ( P＜0.001), respectively. The results of the APC model showed that the average net drift value of leukemia incidence in all age groups was 1.57% (95% CI, 1.24%-1.89%), and the highest value of local drift was 3.20% (95% CI, 1.63%-4.78%) in the 80~ years old group. The incidence of leukemia increased with age. With the passage of time, the risk of leukemia incidence increased gradually compared with the rate ratio of leukemia incidence (risk ratio [ RR], 1.00) in 1992—1996, the RR of leukemia incidence increased from 0.70 during 1972—1976 to 1.57 during 2017—2021. The later the cohort was born, the greater the risk of leukemia incidence compared with the relative risk of leukemia incidence ( RR, 1.00) in 1952—1956 cohort, the RR of leukemia incidence increased from 0.24 in the 1892—1896 cohort to 2.73 in the 2017—2021 cohort. Conclusions:The incidence of the leukemia has presented a rising trend in the past fifty years. Leukemia incidence increased with age, and the period and cohort effects on the risk of incidence increase. Further research is needed to investigate the risk factors related to leukemia.