Objective: To evaluate the anti-fatigue effects of different extracts from Cistanche tubulosa (Schenk) Wight (C. tubulosa, Rou Cong Rong), focusing on central and exercise-induced fatigue in mice. This study investigated the pharmacological effects of the total oligosaccharides, polysaccharides, and phenylethanoid glycosides (CPhGs) extracted from C. tubulosa. Methods: Models of sleep deprivation and forced swimming fatigue were established to simulate central and exercise-induced fatigue. The mice were treated with different extracts of C. tubulosa, and their effects were assessed using behavioral tests to measure exercise capacity, learning, and memory function. Biochemical analyses were performed to evaluate the changes in serum and brain neurotransmitter levels, liver and muscle glycogen storage, and various fatigue-related biomarkers. Results: This study found that treatment with C. tubulosa extract improved exercise capacity, learning, and memory in mice. Total oligosaccharides from C. tubulosa enhanced adrenocorticotropic hormone, cholinesterase, and thyroid-stimulating hormone levels, reduced cortisol levels in central fatigue models, and ameliorated biochemical markers of exercise-induced fatigue, including lowering lactic acid, blood urea nitrogen, and malondialdehyde levels. Among the tested extracts, the total oligosaccharides showed the most comprehensive anti-fatigue effects. Conclusion The anti-fatigue effects of C. tubulosa, particularly those of its total oligosaccharides, are pronounced in both central and exercise-induced fatigue. These effects are mediated by the regulation of neurotransmitter levels, enhancement of glycogen storage, and improvement of antioxidant enzyme activity, suggesting potential therapeutic benefits in fatigue-related conditions.

Objective:To explore the efficacy and safety of the modified VIALE-A regimen in the treatment of elderly (>75 years old) patients with intermediate or high risk myelodysplastic syndromes (MDS).Methods:A retrospective case series analysis was conducted. Clinical data were collected from 7 MDS patients aged >75 years who were continuously treated with the modified VIALE-A regimen (azacytidine 75 mg/m 2 per day from day 1 to day 7 + venetoclax 200 mg per day from day 8 to day 28) from May 2021 to August 2023, and the patients were diagnosed according to the World Health Organization 2016 staging criteria and were determined to be at intermediate or high risk according to the revised International Prognostic Scoring System. The patients' efficacy and common adverse reactions were analyzed, and the Kaplan-Meier method was used for survival analysis. Results:Of the 7 patients, 5 were female and 2 were male; the median age [ M ( Q1, Q3)] was 84 years old (80 years old, 90 years old). One patient failed the initial treatment, and the remaining 6 achieved complete remission or complete remission in bone marrow after induction therapy with the modified VIALE-A regimen in 1-2 courses. By the follow-up cut-off date of December 31st, 2023, the median follow-up was 10 months (5 months, 18 months) and the median overall survival time was 18 months (95% CI: 0-39 months). Grade 3-4 myelosuppression occurred in all 7 patients during the induction phase, with granulocytopenia lasting 7-10 d; Of the 64 courses of maintenance treatment, 54 (84%) had grade 1-3 myelosuppression; non-hematologic adverse reactions were mild; no treatment interruptions occurred in the cumulative 73 courses. Conclusions:The modified VIALE-A regimen is moderately efficacious in elderly patients with intermediate or high risk MDS, with controllable adverse reactions.

Objective This study analyzes the risk points in the quality control of bioink and the main processes of bioprinting,clarifies and explores the quality control and supervision model for bioprinting medical devices,and provides theoretical and practical guidance to ensure the safety and effectiveness of bioprinting medical devices.Methods The quality control risk points throughout the bioprinting process were comprehensively analyzed,with a particular focus on bioprinting materials and key processes.The regulatory model and methods for bioprinting medical devices were examined.This research concentrated on critical technologies such as extrusion,laser-assisted,and in situ bioprinting,assessing their potential for clinical applications and regulatory challenges.Results Bioink from different sources should meet regulatory requirements.It is essential to ensure aseptic handling of raw materials and to validate sterilization under"worst-case"conditions.Conclusion As bioprinting technology advances rapidly,corresponding research into materials,processes,and quality risk control should be conducted to ensure the concurrent development of the regulatory system.This will continuously contribute to the orderly progression of the entire industry and human health.

Cerebral small vessel disease （CSVD） is a common disease with great impact on the health of the Chinese population. CSVD has insidious progression and is often neglected by both patients and physicians. In recent years， advances have been made in the research on CSVD from the aspects of risk factors， pathogenesis， clinical manifestations， and evaluation systems. In 2013， the international Standards for Reporting Vascular Changes on Neuroimaging （STRIVE） collaborative group standardized the definition and description of CSVD， and subsequently in 2021， our team released Chinese expert consensus on the diagnosis and treatment of cerebral small vessel disease 2021， which summarized the latest research findings in China and globally. In 2023， the international STRIVE collaborative group provided further updates on research advances in the field of CSVD. CSVD has similar clinical manifestations to neurodegenerative diseases， with a lack of significant specificity. Although genetic testing and brain tissue biopsy help to make a confirmed diagnosis to a certain extent， their application in clinical practice has been limited by technical and financial constraints. At present， neuroimaging techniques are mainly used to detect brain tissue lesions induced by CSVD and make a diagnosis. This article discusses the imaging markers for the diagnosis of CSVD and the imaging-based differential diagnosis of CSVD.
Diagnosis

Objective:To investigate the clinical outcomes of minimally invasive lateral lumbar interbody fusion (LLIF) and the necessity to perform LLIF plus posterior direct decompression in the treatment of severe degenerative lumbar spinal stenosis (DLSS).Methods:In this prospective randomized, controlled trial, we assigned 71 patients, who were 50 to 80 years old, and diagnosed with severe DLSS (Schizas Classification grade C on magnetic resonance imaging), in a 1∶1 ratio to undergo either one-stage LLIF plus posterior internal fixation (treatment group) or CLIF plus posterior internal fixation with laminectomy (control group). Demographic and perioperative data were collected and compared. The clinical outcome measures included Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ) score as well as visual analogue scale (VAS). Patients were followed up for at least 1 year.Results:The treatment group included 36 patients with 46 surgical levels, while the control group included 35 patients with 46 surgical levels. The baseline demographic data of the 2 groups were equivalent in preoperative central canal areas, spinal canal anteroposterior diameter, disc height, ODI, ZCQ score for symptom severity and physical function, as well as VAS scores for back and leg pain. The mean operative time, blood loss, drainage volume and hospital stay of the treatment group are significantly less than the control group (157.2±29.1 min vs. 180.6±26.8 min, 75.6±39.1 ml vs. 108.6±43.3 ml, 136.9±73.9 ml vs. 220.5±121.3 ml, 5.3±1.1 d vs. 6.6±2.3 d). There were 2 cases with dura tear and 1 case with wound infection in control group. Thus, the surgical trauma and complications of the control group were more than the treatment group. At 1-year follow-up, the mean ODI score of treatment group improved from 42.24%±10.70% preoperatively to 18.21%±11.49%, the mean ZCQ symptom severity from 2.89±0.38 to 1.61±0.41, the mean ZCQ physical function from 2.31±0.45 to 1.50±0.37, the mean VAS for back from 5.56±1.19 to 1.97±1.13 and the mean VAS for leg from 4.44±1.81 to 0.94±1.26. At 1-year follow-up, the mean ODI score of the control group improved from 43.65%±14.93% preoperatively to 17.36%±12.15%, the mean ZCQ symptom severity from 2.92±0.52 to 1.65±0.39, the mean ZCQ physical function from 2.37±0.52 to 1.55±0.39, the mean VAS for back from 5.63±1.40 to 2.34±1.47, and the mean VAS for leg from 4.37±2.14 to 0.83±1.20. The ZCQ satisfactory score of both groups were not significant different (1.25±0.45 vs. 1.26±0.43, t=0.07, P=0.944). The mean improvement rate of both groups for ODI, ZCQ symptom severity, ZCQ physical function, VAS back and VAS leg at 1-year follow-up were not significant different (55.43%±27.74% vs. 58.36%±25.06%, 43.07%±17.22% vs. 42.66%±12.95%, 32.25%±23.65% vs. 31.71%±23.24%, 62.65%±21.25% vs. 58.37%±22.44%, 78.94%±26.41% vs. 85.45%±20.53%). One adjacent segment disease was found in each group at 1 year follow-up. Conclusion:CLIF+ posterior internal fixation in the treatment of Schizas Grade C DLSS has satisfactory clinical outcome at 1-year follow-up. Laminectomy increases surgical trauma, but does not significantly improve the clinical outcome at 1-year follow-up.

ObjectiveTo investigate the protective effect of cytochrome P4502D6 （CYP2D6） and cytochrome P4503A4 （CYP3A4）， key enzymes of drug metabolism in liver， on acute liver injury in water extract of Glycyrrhizae Radix et Rhizoma （WEOGRR）. MethodHealthy male Kunming mice were divided into normal group， model group， WEOGRR low-， medium- and high-dose groups （5， 10， 15 g·kg^-1·d^-1） and positive drug group （diammonium glycyrrhizinate， 75 mg·kg^-1·d^-1）， with 10 in each group. One week after preventive administration， acute liver injury model was induced by single intragastric administration of 270 mg·kg^-1 Tripterygium Glycosides tablets， and samples were collected after 18 h. The pathological changes of liver were observed by hematoxylin-eosin （HE） staining. Serum liver function indexes including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyl transpeptadase （γ-GT）， alkaline phosphatase （ALP）， and total bilirubin （TBIL） as well as the levels of oxidative stress indexes including malondialdehyde （MDA） and superoxide dismutase （SOD） in hepatocytes were determined by biochemical method. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to detect the mRNA and protein expression levels of CYP2D6 and CYP3A4， respectively. ResultCompared with normal group， model group had significant hepatocyte swelling and inflammatory cell infiltration （P<0.01）， increased AST， ALT， γ-GT， ALP and TBIL （P<0.05）， elevated MDA and decreased SOD （P<0.01） as well as down-regulated mRNA and protein expression levels of CYP2D6 and CYP3A4 （P<0.05）. Compared with the model group， the normal group had intact liver structure without obvious abnormality， and the WEOGRR groups and positive drug group presented alleviated hepatocyte swelling and inflammatory cell infiltration （P<0.01）， reduced AST， ALT， γ-GT， ALP and TBIL （P<0.01）， lowered MDA and increased SOD （P<0.01） as well as up-regulated expression levels of CYP2D6 and CYP3A4 （P<0.01）. ConclusionThe protective effect of WEOGRR on acute liver injury induced by Tripterygium glycosides tablets may be related to reducing the contents of AST， ALT， γ-GT， ALP and TBIL in serum， inhibiting MDA and increasing the activity of SOD in liver cells， and enhancing the activities of CYP2D6 and CYP3A4， thus accelerating the metabolism of toxic substances.

OBJECTIVE: To explore the feasibility and early effectiveness of computer-simulated osteotomy based on the health-side combined with guide plate technique in the treatment of cubitus varus deformity in adolescents. METHODS: The clinical data of 23 patients with cubitus varus deformity who met the selection criteria between June 2019 and February 2023 were retrospectively analyzed. There were 17 males and 6 females, ranging in age from 4 to 16 years with an average of 8.5 years. The time from injury to operation was 1-4 years. The angle of distal humerus rotation was defined by humeral head posterior inclination angle using low radiation dose CT to scan the patient's upper extremity data at one time, and the preoperative rotation of the distal humerus on the affected side was (33.82±4.39)°. The CT plain scan data were imported into 9yuan3D digital orthopaedic system (V3.34 software) to reconstruct three-dimensional images of both upper extremities. The simulated operation was performed with the healthy upper extremity as the reference, the best osteotomy scheme was planned, overlapped and compared, and the osteotomy guide plate was prepared. The patients were followed up regularly after operation, and the formation of callus in the osteotomy area was observed by X-ray examination. Before and after operation, the carrying angle of both upper extremities (the angle of cubitus valgus was positive, and the angle of cubitus varus was negative) and anteversion angle were measured on X-ray and CT images. At the same time, the flexion and extension range of motion of elbow joint and the external rotation range of motion of upper extremity were measured, and Mayo score was used to evaluate the function of elbow joint. RESULTS: The operation time ranged from 34 to 46 minutes, with an average of 39 minutes. All patients were followed up 5-26 months, with a mean of 14.9 months. All the incisions healed by first intention after the operation; 2 patients had nail path irritation symptoms after Kirschner wire fixation, which improved after dressing change; no complication such as breakage and loosening of internal fixators occurred after regular X-ray review. Continuous callus formed at the osteotomy end at 4 weeks after operation, and the osteotomy end healed at 8-12 weeks after operation. At last follow-up, the carrying angle, anteversion angle, external rotation range of motion, and extension and flexion range of motion of the elbow joint of the affected side significantly improved when compared with preoperative ones ( P<0.05). Except for the extension range of motion of the healthy elbow joint ( P<0.05), there was no significant difference in other indicators between the two sides ( P>0.05). At last follow-up, the Mayo elbow score was 85-100, with an average of 99.3; 22 cases were excellent, 1 case was good, and the excellent and good rate was 100%. CONCLUSION Computer-simulated osteotomy based on health-side combined with guide plate technique for treating cubitus varus deformity in adolescents can achieve precise osteotomy, which has the advantages of short operation time and easy operation, and the short-term effectiveness is satisfactory.
Male ; Female ; Humans ; Adolescent ; Child, Preschool ; Child ; Elbow ; Humeral Fractures/surgery* ; Retrospective Studies ; Joint Deformities, Acquired/surgery* ; Elbow Joint/surgery* ; Limb Deformities, Congenital ; Osteotomy/methods* ; Humeral Head ; Range of Motion, Articular ; Computers ; Treatment Outcome

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40％of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.

Objective:To investigate the influence of different degrees of facet joint arthropathy on the indirect decompression effect of crenel lumbar interbody fusion (CLIF), and the clinical outcomes of CLIF for the treatment of lumbar spinal stenosis with severe facet joint arthropathy (grade 3).Methods:This study reviewed a total of 269 surgical segments in 156 patients with lumbar spinal stenosis treated with CLIF technique from November 2016 to February 2020. According to preoperative CT images, the facet joint was graded according to Pathria classification. There are 19 segments with grade 0, 156 segments with grade 1, 67 segments with grade 2, and 27 segments with grade 3. Radiographic parameters included disc angle, anterior and posterior disc height, and bilateral intervertebral foramen height on CT, and the midsagittal canal diameter and axial central canal area. In 30 patients with at least one segment of grade 3, the clinical efficacy was assessed using visual analogue scale (VAS) and Oswestry disability index (ODI).Results:The average the anterior and posterior intervertebral space height, intervertebral space angle, height of bilateral intervertebral foramina, spinal canal sagittal diameter and spinal canal area were significantly improved after the operation of grade 3 facet joint degeneration segment compared to preoperation. The preoperative mean spinal canal sagittal diameter and spinal canal area of grade 3 facet joint degeneration segment were significantly less than grade 1 and grade 2. The average change of spinal canal area after grade 3 articular degeneration was significantly less than that of grade 1 and 2, but there was no significant difference with that of grade 0. The posterior decompression rate was 55.56% (15/27) for grade 3, 35.82% (24/67) for grade 2, 16.03% (25/156) for grade 1, and 21.05% (4/19) for grade 0. The posterior decompression rate of grade 3 articular process degeneration was significantly higher than that of other grades ( P<0.001). Severe lateral recess stenosis and 24.24% of severe intervertebral foraminal stenosis were found in 81.48% of grade 3 degenerative segment. The 23 patients were followed up with an average of 21.62±6.52 months, and the average improvement of ODI was 24.10%±11.09%; the average VAS for leg pain and back pain were improved significantly. Conclusion:The degrees of facet joint degeneration do not prevent intervertebral space distraction of CLIF. However, because segments with severe facet joint arthropathy were usually associated with severe spinal canal stenosis, CLIF had a high rate of second-stage posterior decompression in the treatment of lumbar spinal stenosis with severe facet joint arthropathy.

Malaria is an ancient infectious disease that threatens millions of lives globally even today. The discovery of artemisinin, inspired by traditional Chinese medicine (TCM), has brought in a paradigm shift and been recognized as the "best hope for the treatment of malaria" by World Health Organization. With its high potency and low toxicity, the wide use of artemisinin effectively treats the otherwise drug-resistant parasites and helps many countries, including China, to eventually eradicate malaria. Here, we will first review the initial discovery of artemisinin, an extraordinary journey that was in stark contrast with many drugs in western medicine. We will then discuss how artemisinin and its derivatives could be repurposed to treat cancer, inflammation, immunoregulation-related diseases, and COVID-19. Finally, we will discuss the implications of the "artemisinin story" and how that can better guide the development of TCM today. We believe that artemisinin is just a starting point and TCM will play an even bigger role in healthcare in the 21st century.
Artemisinins/therapeutic use* ; COVID-19/drug therapy* ; Drug Repositioning ; Humans ; Medicine, Chinese Traditional ; Neoplasms/drug therapy*