BACKGROUND:Previous studies have confirmed that Wen-Shen-Tong-Du Decoction can promote the recovery of spinal cord injury by inhibiting pyroptosis of splenic B cells,promoting the phagocytosis of myelin debris by microvascular endothelial cells,affecting the migration and infiltration of microglia,promoting the recovery of damaged neurons,and decreasing neuronal apoptosis after spinal cord injury,but the mechanism of this is still not clear. OBJECTIVE:To investigate the effect of Wen-Shen-Tong-Du Decoction on the triggering receptor expressed on myeloid cells 2(TREM2)and PI3K/Akt signaling pathways in mice following spinal cord injury. METHODS:Thirty-six C57BL/6 mice were selected and randomly divided into a sham-operation group,a model group and a Wen-Shen-Tong-Du Decoction group,with 12 mice in each group.In the model and Wen-Shen-Tong-Du Decoction groups,mouse models of T10 spinal cord injury were prepared by the modified Allen's method.On the 1st day after modeling,the Wen-Shen-Tong-Du Decoction group was given Wen-Shen-Tong-Du Decoction by gavage,and the sham-operation group and the model group were given saline by gavage once a day for 28 days.During the drug administration period,mouse motor function was evaluated by Basso Mouse Scale score and inclined plane test.On the 7th and 28th days after modeling,hematoxylin-eosin staining was used to observe the histopathological changes in the spinal cord tissue of the mice;immunofluorescence double staining was used to detect the protein expression of ionized calcium binding adaptor molecule 1(IBA1)and TREM2;and western blot assay was used to detect the expression of TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,Bax and Caspase3 in spinal cord tissue. RESULTS AND CONCLUSION:Basso Mouse Scale scores and inclined plane test results indicated that the motor function of the mouse hindlimbs was declined after spinal cord injury,and Wen-Shen-Tong-Du Decoction significantly improved motor function in mice with spinal cord injury.Hematoxylin-eosin staining results revealed that Wen-Shen-Tong-Du Decoction significantly ameliorated the pathological structure of spinal cord tissue compared with the model group,manifesting as reduced degrees of dorsal white matter and neuronal atrophy,decreased cytoplasmic vacuolization,and reduced inflammatory cell infiltration.Immunofluorescence double staining results showed that on the 7th day after modeling,the protein expression of IBA1 and TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of IBA1 and TREM2 in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05);on the 28th day after modeling,the protein expression of TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of TREM2 in the spinal cord tissue of the mice in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05).Western blot results analysis demonstrated that on the 7th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,and Bcl2/Bax(P＜0.05),as well as a significant increase in p-Akt,Bax and p-Akt/Aktp-PI3K(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,p-PI3K/PI3K,p-Akt/Ak,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax and Caspase3 protein expression(P＜0.05).On the 28th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2 and Bcl2/Bax(P＜0.05),as well as a significant increase in Bax protein expression(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,Akt,p-Akt,Bcl2,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax protein expression(P＜0.05).To conclude,Wen-Shen-Tong-Du Decoction may activate the PI3K/Akt signaling pathway by up-regulating the expression of TREM2 protein in microglia,and then inhibit neuronal apoptosis,thus exerting neuroprotective effects and promoting the repair of spinal cord injury.

BACKGROUND:It has been proved clinically that adhesion of fibrous scar with the dura mater or nerve root after lumbar operation is an important factor for postoperative symptoms,such as postoperative pain and numbness. OBJECTIVE:To verify the inhibitory effect of autologous ligamentum flavum on the formation of epidural fibrous scar after lumbar surgery and explore the possible molecular biological mechanism. METHODS:Forty-eight Japanese white rabbits(6-8 months old)were randomly divided into three groups:a ligamentum flavum preservation group,a ligamentum flavum non-preservation group,and an autologous fat reposition group.A lumbar laminectomy model was established in all the three groups of rabbits,and rabbit epidural tissues were collected at 3 and 6 weeks after modeling.Hematoxylin-eosin staining was used to observe histological changes and the number and density of fibroblasts,VG staining was used to observe the percentage of collagen fiber area,and immunohistochemistry was used to observe the expression of transforming growth factor β1 and Smad3 proteins. RESULTS AND CONCLUSION:Hematoxylin-eosin staining results revealed that fibroblasts in the ligamentum flavum preservation group were few and loosely arranged,while the cells in the ligamentum flavum non-preservation and autologous fat reposition groups were more numerous and closely arranged.The number density of fibroblasts in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery(P＜0.05);however,there was no significant difference between the latter two groups.VG staining results showed that the collagen fibers in the ligamentum flavum preservation group were sparse and distributed unevenly,while a lot of red collagen fibers were gathered in the ligamentum flavum non-preservation and autologous fat reposition groups.The area percentage of collagen fibers in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery(P＜0.05),but there was no significant difference between the latter two groups.The results of immunohistochemistry showed that the degree of positive staining of retained histone the ligamentum flavum preservation group was significantly lower than that of the other two groups.The absorbance value of transforming growth factor β1 and Smad3 in the ligamentum flavum preservation group was significantly lower than that in the other two groups at 3 and 6 weeks after surgery(P＜0.05),but there was no significant difference between the latter two groups.To conclude,there are different degrees of epidural fibrous scar formation after lumbar surgery.If the ligamentum flavum is preserved,it can help to reduce the number of epidural fibroblasts as well as the formation of collagen fibers,thus reducing the adhesion of the fibrous scar tissue to the dural sac and nerve root.The mechanism is not only a purely mechanical blockade,but also to reduce the formation of epidural fibrous scar by interfering with the transforming growth factor β1/Smad3 signaling pathway.

BACKGROUND:Successful uterine spiral artery remodeling is necessary for normal pregnancy,in which vascular smooth muscle cells are important cells.Interferon-γ is associated with the loss of vascular smooth muscle cells during early pregnancy.However,the specific mechanism is not fully understood. OBJECTIVE:To investigate the effects of interferon-γ on migration and apoptosis of vascular smooth muscle cells through NLRP3/caspase-1/GSDMD pyroptosis pathway. METHODS:Human vascular smooth muscle cells were divided into control group and interferon-γ group.The control group was cultured normally,and the interferon-γ group was treated with 10 ng/mL interferon-γ for 24 hours.The migration ability of vascular smooth muscle cells was detected by Transwell assay.The apoptosis of vascular smooth muscle cells was detected by TUNEL assay and flow cytometry.The mRNA expression levels of NLRP3 and caspase-1 were detected by qPCR.Western blot assay was utilized to detect NLRP3,caspase-1,and cleaved N-terminal GSDMD protein expression levels. RESULTS AND CONCLUSION:Compared with the control group,the migration ability and apoptosis rate of vascular smooth muscle cells in interferon-γ group were significantly increased(P<0.05).Compared with the control group,the mRNA expression levels of NLRP3 and caspase-1 in vascular smooth muscle cells of interferon-γ group were significantly increased(P<0.05).Compared with control group,the expression levels of NLRP3,caspase-1,and cleaved N-terminal GSDMD protein in vascular smooth muscle cells in the interferon-γ group were significantly increased(P<0.05).The results suggest that interferon-γ may regulate the migration and apoptosis of vascular smooth muscle cells through NLRP3/caspase-1/GSDMD pyroptosis pathway.

BACKGROUND:Dental pulp stem cells are one of the stem cells with great potential in oral and maxillofacial tissue engineering.Compared with mesenchymal stem cells,dental pulp stem cells have the advantages of convenient collection,less ethical problems and higher potential of proliferation and differentiation.Currently,except for biochemical factors,physical stimulation also plays a critical role in the osteogenic/odontogenic differentiation of dental pulp stem cells. OBJECTIVE:To review the relevant physical factors and the possible signaling pathway affecting the osteogenic/odontogenic differentiation of dental pulp stem cells to find the optimal induction conditions affecting their differentiation. METHODS:PubMed and CNKI databases were searched for relevant articles using"dental pulp stem cells(DPSCs),osteogenesis differentiation,odontoblastic differentiation,hypoxia,mechanical force,laser therapy,magnetic fields,microgravity"as English and Chinese search terms.Seventy-nine articles regarding physical factors affecting osteogenic/odontogenic differentiation of dental pulp stem cells were selected for the review. RESULTS AND CONCLUSION:(1)Direct or indirect physical signals in the microenvironment have shown broad application prospects in regulating the directed differentiation of stem cells.Many related physical factors,for example,hypoxia,mechanical stimulation(dynamic hydrostatic pressure,mechanical tension,shear force,etc.),laser,microgravity,and magnetic field,have positive influences on the osteogenic/odontogenic differentiation of dental pulp stem cells.Owing to the complex mechanical environment of stomatognathic system,mechanical stimulation is a key physical factor in changing cellular environment and is also a frontier in tissue engineering.It will provide new ideas for investigating the response of dental pulp stem cells to the mechanical environment in the diagnosis and treatment of oral diseases.(2)Because this field is relatively"young",the parameters of equipment have not been unified and the relevant results are not consistent.The optimal induction parameters and conditions of related physical factors should be further explored and optimized.(3)Scaffold material,one of the three elements of tissue engineering,plays a role in promoting the osteogenic/odontogenic differentiation of dental pulp stem cells,and promotes the development of materials science and clinical technology.(4)The signaling pathways involve Notch,Wnt,MAPK,etc.The biological basis of regulating the behavior of dental pulp stem cells is not clear.The specific mechanism will be further explored in the future to provide new ideas for dental pulp regeneration and bone tissue engineering under the influence of physical factors.

OBJECTIVE:This paper collects relevant literature on blood flow restriction training combined with resistance training,and analyzes the different effects of blood flow restriction training combined with resistance training on athletes'muscle-related indexes and specialized abilities in accordance with the paradigm of systematic evaluation and Meta-analysis,aiming to provide data support for athletes to utilize blood flow restriction training in their training practices. METHODS:Chinese and foreign databases(CNKI,WanFang,PubMed,Web of Science,SPORTDiscus)were searched to collect randomized controlled trials on the effects of blood flow restriction training combined with resistance training on limb circumference,muscle mass,muscle strength,and specialized ability of college athletes from January 1st,2000 to October 12th,2023.At least two researchers evaluated the quality of the included literature using the Cochrane Collaboration risk of bias assessment tools and criteria.Heterogeneity tests,data merging,subgroup analyses,forest plotting,and sensitivity analyses were performed using RevMan 5.4,and funnel plots with publication bias evaluation and sensitivity analyses were performed.The evaluation indexes were limb circumference,muscle thickness,muscle strength and specialized ability,and subgroup analyses were performed for different specialized athletic abilities. RESULTS:(1)A total of 18 randomized controlled trials with 403 subjects were included,and according to the Cochrane Collaboration's risk of bias assessment tool,the quality of literature in the included literature was grade A in 16 articles and grade B in 2 articles.(2)Comparing the effects of blood flow restriction training combined with resistance training and resistance training,there was no significant difference between the two groups in terms of limb circumference[standardized mean difference(SMD)=0.03,95%confidence interval:-0.16-0.21,P=0.78],and a significant difference between the two groups in terms of muscle thickness(SMD=0.14,95%CI:0.01-0.27,P=0.03)and muscle strength(SMD=0.37,95%CI:0.14-0.60,P=0.001).(3)Subgroup analyses of the indicators of specialized capacity indicated that there was high heterogeneity in the analyzed results of distance metrics(I2=73%)and time metrics(I2=55%),which was analyzed as a possible reason due to the differences in testing methods and assessment of metrics'significance in the studies;there was no heterogeneity(I2=0%)in the analyzed results of power metrics;blood flow restriction training combined with resistance training had a significant effect on distance metrics(P<0.01).(4)The results of the combined effect showed the effect of blood flow restriction training combined with resistance training vs.resistance training for specialized ability(P=0.41),suggesting that there is no significant effect of different training methods on specialized ability. CONCLUSION:Both blood flow restriction training combined with resistance training and resistance training can promote muscle thickness,muscle strength and specialized ability in college athletes.Meanwhile,blood flow restriction training combined with resistance training has a more significant effect on muscle thickness,muscle strength and some specialized abilities compared with resistance training.Therefore,blood flow restriction training can be scientifically and rationally integrated into specialized training,so as to achieve a better training effect by integrating the differentiated physiological stimuli to the muscles.However,due to the small number of included studies and other possible limitations,more high-quality,multi-sport type and sex randomized trials need to be included in the future to confirm this.

Chronic fatigue syndrome (CFS) is a common problem in military maritime navigation, which greatly affects the safety of military missions. The use of animal models to carry out research on the mechanism of CFS and treatment measures is a common method. This paper systematically introduced the construction methods of CFS models such as single-factor and multi-factor models, summarized common evaluation indicators of CFS, including behavioral and biochemical indicators, and summed up key characteristics of CFS animal models in military oceanic navigation combined with common causes of CFS in military contexts, such as prolonged continuous work, high-intensity physical activity, sleep deprivation, psychological stress, and extreme environmental conditions. The key characteristics of the animal models included, but not limited to, chronic fatigue, sleep disorders, impaired cognitive function, psychological stress responses, and abnormal biochemical indicators. Furthermore, this article identified future research directions for CFS animal models in military oceanic navigation to enhance the application value of the models and provide robust support for the health protection and disease prevention of military personnel.

The effectiveness and professionalism of hospice care services for children with cancer are of great significance for improving their quality of life and reducing the mental and economic burden on their families. Currently， a relatively complete quality evaluation system for hospice care for children with cancer has been established abroad， while research in this field in China is still in its infancy. By elaborating on the concept and connotation of quality assessment of hospice care for children with cancer in detail， systematically reviewing the research status of quality assessment of hospice care for children with cancer abroad， and addressing the problems and challenges faced by quality assessment of hospice care for children with cancer in China， corresponding inspirations and improvement strategies were proposed， aiming to provide a reference for improving the quality of hospice care for children with cancer in China.

OBJECTIVE To provide a reference for individualized treatment and pharmaceutical care for patients with breast cancer complicated with chronic kidney disease （CKD）. METHODS Clinical pharmacists participated in the anti-tumor treatment and pharmaceutical care for a breast cancer patient with CKD. Clinical pharmacists reviewed guidelines and literature to assist the clinical physician in formulating the initial neoadjuvant treatment plan （docetaxel+trastuzumab+paltuzumab） and provided monitoring recommendations for potential adverse drug reactions， such as vomiting， myelosuppression， renal impairment， cardiotoxicity. In response to the patient’s acute kidney injury after treatment， clinical pharmacists assisted the physician in analyzing the cause of the adverse reaction through causality assessment. Taking into account the patient’s preferences， docetaxel was substituted with paclitaxel （which did not require dose adjustment based on renal function）. The clinical pharmacists collaborated with the physician to establish a postoperative targeted therapy regimen （trastuzumab+pertuzumab）. Taking into account the patient’s positive estrogen receptor status， the clinical pharmacists recommended to initiate regular anastrozole administration after the completion of radiotherapy and undergo periodic bone density assessments. RESULTS The clinical physician accepted the suggestions from the clinical pharmacists. The patient successfully completed preoperative neoadjuvant chemotherapy and postoperative targeted therapy， and was discharged with medication （anastrozole）. During the treatment process， the patient did not experience adverse reactions such as myelosuppression， cardiotoxicity， or the occurrence of osteoporosis. CONCLUSIONS Clinical pharmacists analyzed and adjusted the preoperative and postoperative antitumor treatment plans based on the patient’s renal function. They promptly assessed the correlation between antitumor drugs and acute kidney injury， and actively implemented comprehensive pharmaceutical care to ensure medication safety for breast cancer patients with CKD.

Portal vein thrombosis (PVT) is one of the most common complications of liver cirrhosis. The formation of PVT can increase the mortality rate of cirrhotic patients and adversely affect the successful implementation and prognosis of liver transplantation. A hypercoagulable state is a unique mechanism underlying PVT formation in cirrhotic patients. In recent years, the pathogenesis of PVT has gradually been elucidated, with specific mechanisms including the following aspects: systemic and local inflammatory responses lead to vascular endothelial cell dysfunction, thereby promoting the activation of the coagulation system; abnormal activation of the monocyte-macrophage system exacerbates local inflammation, enhancing platelet adhesion and aggregation, and facilitating thrombus formation; an imbalance between the coagulation and fibrinolytic systems results in a sustained hypercoagulable state; and intestinal microbiota dysbiosis induces inflammation and metabolic disturbances, thereby increasing the risk of PVT. This article summarizes the latest research progress on these key mechanisms and their interactions, providing new insights into the molecular and cellular mechanisms of PVT. It also offers directions for the early diagnosis of PVT and the exploration of novel intervention strategies in the future.

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.