BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

BACKGROUND:Acupoint embedding and floating needle therapy are two methods for the treatment of knee osteoarthritis,but there are few reports on the combined treatment of the two methods. OBJECTIVE:To investigate the therapeutic effect of acupoint embedding combined with floating needle therapy on different stages of knee osteoarthritis using generalized estimating equations. METHODS:A total of 436 patients with knee osteoarthritis admitted to Dongguan Hospital of Traditional Chinese Medicine from February 2019 to February 2023 were selected as the research subjects.All patients were randomly divided into a control group with floating needle therapy(n=218)and an observation group with acupoint embedding method combined with floating needle therapy(n=218).Staging was performed according to the K-L staging method.In the control group,there were 57 cases in stage Ⅰ,62 in stage Ⅱ,49 in phase Ⅲ,and 50 in stage Ⅳ,while in the observation group,there were 48 cases in stage Ⅰ,66 in stage Ⅱ,63 in phase Ⅲ,and 41 in stage Ⅳ.The levels of indexes and clinical efficacy were compared between groups before and after treatment.Generalized estimating equation model was used to analyze the influencing factors of clinical efficacy and the interaction effect of different time points,different methods and different stages on therapeutic efficacy. RESULTS AND CONCLUSION:There was no significant difference in baseline data between the observation group and the control group,as well as between the patients of different stages(P>0.05).After treatment,the cure rate of stage Ⅰ patients was the highest after treatment,and the total improvement rate in the observation group was significantly higher than that in the control group.There were significant differences in the cure rate among different stages in each group(P<0.05).After treatment,all indicators in the two groups were significantly decreased.In the control group,there were significant differences in various indicators of patients at different stages after 4 weeks of treatment(P<0.05).In the observation group,after 2 weeks of treatment,there were significant differences in various indicators of patients at different stages(P<0.05),and all the indexes in the observation were lower than those in the control group after 4 weeks of treatment(P<0.05)and the therapeutic effect in the observation group was better than that in the control group.Generalized estimating equation model analysis showed that trauma history,interleukin-6 level,treatment method,treatment time and K-L stage all significantly affected the clinical efficacy in patients.In the interaction effect analysis,after 2 weeks of treatment,there was a significant difference in the visual analogue scale score between the two groups in stages Ⅲ and Ⅳ(P<0.05).After 4 weeks of treatment,there was a significant difference in the visual analogue scale score between the two groups in stages Ⅱ,Ⅲ,and Ⅳ(P<0.05).To conclude,acupoint embedding combined with floating needle therapy is superior to floating needle therapy alone in the treatment of different stages of knee osteoarthritis.Trauma history,interleukin-6 level,treatment method,treatment time and K-L stage significantly influence the therapeutic effect.

In 2023,the U.S.Defense Advanced Research Projects Agency(DARPA)continued to advance the deployment of biotechnology projects.By translating cutting-edge biotechnological breakthroughs into practical applications,DARPA provided new methods to enhance the U.S.military capabilities in treating war wounds,improving the performance of facilities and equipment,and boosting soldier effectiveness.This paper offers an in-depth analysis of the progress of DARPA biotechnology projects in 2023,aiming to provide reference for related research endeavors in China.

In 2024,the U.S.Defense Advanced Research Projects Agency(DARPA)intensified its deployment and management of biotechnological defense applications that involved four major domains:combat effectiveness enhancement,biosecurity defense,development of military materials,and intelligent biotechnology.This paper conducts an in-depth analysis of DARPA's 2024 biotech advancements to provide a reference for related research and development in China.

Heart failure (HF) is a common end-stage clinical manifestation of cardiovascular diseases, imposing substantial health-related burdens worldwide. With its high mortality rates and poor long-term prognosis, there is a pressing need for novel therapies. SIRT1, a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase, has anti-cardiovascular aging properties and other cardioprotective effects, attracting much research attention in recent years. In addition, SIRT1 plays an important role in HF pathophysiology. This review summarized the roles of SIRT1 and its activators in HF, the changes of SIRT1 gene expression in cardiac tissues from animal models and HF patients, and the current status of clinical trials investigating SIRT1 activators as potential therapies for HF. This will provide new ideas for further exploration of pathological mechanisms and the development of clinical prevention strategies for HF.
Heart Failure/metabolism* ; Sirtuin 1/genetics* ; Humans ; Animals

This study primarily investigates the effect of Liuwei Dihuang Pills on the activation and proliferation of female germline stem cells(FGSCs) in the ovaries and cortex of mice with premature ovarian failure(POF), and how it improves ovarian function. ICR mice were randomly divided into the control group, model group, Liuwei Dihuang Pills group, Liuwei Dihuang Pills double-dose group, and estradiol valerate group. A mouse model of POF was established by intraperitoneal injection of cyclophosphamide. After successful modeling, the mice were treated with Liuwei Dihuang Pills or estradiol valerate for 28 days. Vaginal smears were prepared to observe the estrous cycle and body weight. After the last administration, mice were sacrificed and sampled. Serum levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-Müllerian hormone(AMH) were measured by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe ovarian morphology and to count follicles at all stages to evaluate ovarian function. Immunohistochemistry was used to detect the expression of mouse vasa homolog(MVH), a marker of ovarian FGSCs. Immunofluorescence staining, using co-labeling of MVH and proliferating cell nuclear antigen(PCNA), was used to detect the expression and localization of specific markers of FGSCs. Western blot was employed to assess the protein expression of MVH, octamer-binding transcription factor 4(Oct4), and PCNA in the ovaries. The results showed that compared with the control group, the model group exhibited disordered estrous cycles, decreased ovarian index, increased atretic follicles, and a reduced number of follicles at all stages. FSH and LH levels were significantly elevated, while AMH and E_2 levels were significantly reduced, indicating the success of the model. After treatment with Liuwei Dihuang Pills or estradiol valerate, hormone levels improved, the number of atretic follicles decreased, and the number of follicles at all stages increased. MVH marker protein and PCNA proliferative protein expression in ovarian tissue also increased. These results suggest that Liuwei Dihuang Pills regulate estrous cycles and hormone disorders in POF mice, promote the proliferation of FGSCs, improve follicular development in POF mice, and enhance ovarian function.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cell Proliferation/drug effects* ; Mice, Inbred ICR ; Ovary/cytology* ; Primary Ovarian Insufficiency/genetics* ; Follicle Stimulating Hormone/metabolism* ; Humans ; Anti-Mullerian Hormone/blood* ; Antineoplastic Agents/adverse effects* ; Luteinizing Hormone/metabolism* ; Cyclophosphamide/adverse effects*

OBJECTIVE: To explore the effectiveness of the flexor digitorum longus (FDL) transfer combined with single-bundle spring ligament reconstruction and medial displacement calcaneal osteotomy in the treatment of stage ⅠAB progressive collapsing foot deformity (PCFD). METHODS: Between January 2019 and September 2023, 19 patients (19 feet) with stage ⅠAB PCFD were treated with FDL transfer combined with single-bundle spring ligament reconstruction and medial displacement calcaneal osteotomy. There were 11 males and 8 females, aged 18 to 60 years, with an average age of 45.5 years. Nine cases were on the left foot and 10 cases on the right foot. The disease duration was 9-21 months, with an average of 12.3 months. Postoperatively, the effectiveness was evaluated by visual analogue scale (VAS) for pain, American Orthopaedic Foot and Ankle Society (AOFAS) score, and Tegner score. Based on X-ray films, the talonavicular coverage angle (TNCA), talus-first metatarsal angle (T1MT), Meary angle, and pitch angle were measured. The plantar pressure parameters of the foot were measured by the Footscan plantar pressure measurement system, including peak pressure and load of the forefoot, midfoot, and hind foot. The patients' satisfaction with the surgical outcome was evaluated. RESULTS: All 19 surgeries were successfully completed. One patient had poor incision healing after operation, while the incisions of the remaining patients healed by first intention. All patients were followed up 12-28 months (mean, 16.8 months). At last follow-up, the VAS score significantly decreased compared with that before operation, and the AOFAS score and Tegner score significantly increased ( P<0.05). Radiological measurements showed that the TNCA, T1MT, Meary angle, and Pitch angle all significantly improved compared with those before operation ( P<0.05). Plantar pressure tests indicated that the peak pressures of the forefoot and midfoot significantly reduced compared with those before operation ( P<0.05), while the peak pressure of the hind foot showed no significant change ( P>0.05). The forefoot load significantly increased and the midfoot load decreased compared with those before operation ( P<0.05), while the hind foot load showed no significant change ( P>0.05). The total satisfaction rate of patients with the surgical outcome (very satisfied+satisfied) reached 84.2% (16/19). CONCLUSION The FDL transfer combined with single-bundle spring ligament reconstruction and medial displacement calcaneal osteotomy can effectively correct the stage ⅠAB PCFD, improve the abnormal distribution of plantar pressure and load, alleviate foot pain symptoms, and improve foot movement function. The patient's satisfaction is high. However, the long-term effectiveness still needs to be further observed and clarified.
Humans ; Female ; Male ; Osteotomy/methods* ; Adult ; Middle Aged ; Calcaneus/surgery* ; Young Adult ; Adolescent ; Tendon Transfer/methods* ; Treatment Outcome ; Plastic Surgery Procedures/methods* ; Foot Deformities/surgery* ; Ligaments, Articular/surgery*

OBJECTIVE: Objective To investigate the relationship between cervical disc herniation and C₀-C₂ Cobb angle. METHODS: The clinical data of 301 patients with cervical disc herniation from 2020 to 2024 were retrospectively analyzed. The median value of C₀-C₂ Cobb angle measurements from 301 patients was used as the boundary, cervical disc herniation patients were divided into two groups, C₀-C₂ Cobb angle <28.50 group and 151 patients with C₀-C₂ Cobb angle≥28.50 group. Among them, 150 patients in C₀-C₂ Cobb angle <28.50 group included 53 males and 97 females, aged 23 to 76 (57.32±12.55) years, with a disease duration of 7 to 19 (13.81±5.32) months;the othor 151 patients with C₀-C₂ Cobb angle≥28.50 group including 61 males and 90 females, aged 25 to 74 (56.86±12.51) years, with a disease duration of 8 to 18 (14.13±5.56) months. The cervical lordosis angle (C₀-C₂ Cobb angle and C₂-C₇ Cobb angle), T₁ inclination slope (T₁S) and cervical sagittal axial distance (C₂-C₇ SVA) were measured on the lateral cervical radiographs. The correlation between C₀-C₂ Cobb angle and cervical disc herniation range, protrusion position, average protrusion size and other parameters was analyzed. RESULTS: When the C₀-C₂ Cobb angle<28.50°, the average protrusion size was (2.21±0.56) mm, the C₂-C₇ Cobb angle was (19.92±12.06)° and the C₂-C₇ SVA was (1.10±1.20) mm. When the C₀-C₂ Cobb angle≥28.50°, the average protrusion size was (2.38±0.60) mm, the C₂-C₇ Cobb angle was (12.01±13.09 )°, the C₂-C₇ SVA was (1.53±1.36) mm, and the difference was statistically significant (P<0.05). Between the two groups of patients with C₀-C₂ Cobb angle < 28.50° and C₀-C₂ Cobb angle≥28.50°, there were significant differences in the size of C_3,4, C_4,5, C_5,6, C_6,7, C₇, T₁ disc herniation in single segment (P<0.05 ). C₀-C₂ Cobb angle was correlated with age(r=-0.135, P<0.05 ), C₂-C₇ Cobb angle (r=-0.382, P<0.01 ), C₂-C₇ SVA (r=0.293, P<0.01), average protrusion size (r=0.139, P<0.05), and the size of C_3,4 (r=0.215, P<0.01 ), C_4,5 (r=0.176, P<0.01 ), C_5,6 (r=0.144, P<0.05 ), C_6,7 (r=0.158, P<0.05 ), C₇T₁ (r=0.535, P<0.05) disc herniation. CONCLUSION There is a positive correlation between C₀-C₂ Cobb angle and the size of cervical disc herniation. C₀-C₂ Cobb angle can reflect the degree of cervical disc herniation. Previous studies have shown that the biomechanical changes between C₀-C₂ Cobb angle, C₂-C₇ Cobb angle, C₂-C₇ SVA and cervical extensor muscle group may be risk factors for accelerating cervical disc herniation and this may be one of the mechanisms that C₀-C₂ Cobb angle is positively correlated with the size of cervical disc herniation.
Humans ; Male ; Female ; Middle Aged ; Intervertebral Disc Displacement/physiopathology* ; Adult ; Cervical Vertebrae/diagnostic imaging* ; Aged ; Retrospective Studies ; Young Adult

Infancy is a critical period for children's growth and development. During this period，the reasonable increase of fat mass percentage and fat mass index is very important for children's healthy growth. However，excessive increases in fat mass percentage and fat mass index may increase the risk of metabolic related diseases. In China，the research field of body composition in infants is still in the development stage，and the relevant research results and literature are relatively few. This article summarizes the domestic and foreign research on infant body composition，including application techniques，influencing factors and application significance，so as to provide reference for the formulation of domestic infant body composition reference standards and related clinical and scientific research work.

Objective To evaluate the clinical efficacy of tendon-regulating and bone-setting manipulation combined with subtalar joint arthroereisis in the treatment of adolescent flexible flatfoot.Methods A retrospective analysis was conducted on the clinical data of 86 children with flexible flatfoot treated at Dongguan Hospital of Guangzhou University of Chinese Medicine(Dongguan Traditional Chinese Medicine Hospital)between December 2022 and February 2024.Based on pre-treatment physician-patient communication,the children were divided into an trial group(44 cases)and a control group(42 cases).The control group received subtalar joint arthroereisis alone,while the trial group received additional tendon-regulating and bone-setting manipulation just once one day before surgery and once weekly postoperatively for one month,with a follow-up period of no less than 6 months.The Visual Analogue Scale(VAS)pain score,American Orthopaedic Foot & Ankle Society(AOFAS)ankle-hindfoot score,Tegner activity score,radiographic parameters,and static plantar pressure parameters of the two groups were observed before and after surgery.Results(1)Regarding clinical data,all surgeries were successfully completed in both groups.There were no statistically significant differences in perioperative general data,including operative time,hospital stays,and complication rates(P＞0.05).All children were followed up for no less than 6 months.The results showed that at the final follow-up,the VAS pain score,AOFAS ankle-hindfoot score,and Tegner activity score were significantly improved in both groups compared to preoperative values(P＜0.05),and the improvement in the trial group was significantly greater than that in the control group(P＜0.05 or P＜0.01).(2)Regarding radiographic parameters,at the final follow-up,the talonavicular coverage angle(TNCA),talus-first metatarsal angle(T1MT),talus-second metatarsal angle(T2MT)on weight-bearing anteroposterior radiographs,and the Meary angle between the talus and the first metatarsal as well as calcaneal Pitch angle(Pitch angle)on weight-bearing lateral radiographs were significantly improved in both groups compared to preoperative values(P＜0.05).The improvement in Meary angle,T1MT angle,and T2MT angle in the trial group was significantly greater than that in the control group(P＜0.01).However,there were no statistically significant differences in TNCA and Pitch angle between the two groups at the final follow-up(P＞0.05).(3)Regarding plantar pressure testing,at the 1-month postoperative follow-up,the forefoot load increased significantly in both groups compared to preoperative values(P＜0.05),while the midfoot load significantly decreased(P＜0.05).The increase in forefoot load and decrease in midfoot load in the trial group were significantly greater than those in the control group(P＜0.05 or P＜0.01).However,there were no statistically significant differences in hindfoot load between preoperative and postoperative values or between the two groups at the 1-month follow-up(P＞0.05).Conclusion For adolescent flexible flatfoot,tendon-regulating and bone-setting manipulation combined with subtalar joint arthroereisis can effectively restore the arch,improve foot mechanical imbalance,thereby correcting flatfoot deformity and enhancing joint motor function.