ObjectiveTo elucidate the efficacy connotation of Shudi Qiangjin pills （SQP） against liver and kidney deficiency in steroid-induced osteonecrosis of femoral head （SONFH） from the perspective of the "disease-syndrome-formula" association and to clarify the underlying mechanisms based on in vivo and in vitro experiment validation. MethodsThe chemical components and the corresponding putative targets of SQP were collected from the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0， the Encyclopedia of Traditional Chinese Medicine （ETCM） v2.0， and HERB databases. The SONFH-related genes were identified based on the differential expression profiles of peripheral blood of patients with SONFH compared to the healthy volunteers， and the disease phenotype-related targets were collected from the TCMIP v2.0 database. Then， the interaction network of "SONFH-related genes and candidate targets of SQP" was constructed based on "gene-gene interaction information"， and the major network targets were screened by calculating the topological characteristic values of the network followed by the functional mining according to the Kyoto Encyclopedia of Genes and Genomes （KEGG） database and the SoFDA database. After that， the SONFH rat model was prepared by lipopolysaccharide combined with methylprednisolone injection， and 2.5， 5， 7.5 g·kg^-1 SQP （once per day， equivalent to 1， 2， and 3 times the clinical equivalent dose， respectively） or 7.3×10^-3 g·kg^-1 of alendronate sodium （ALS， once per week， equivalent to the clinical equivalent dose） was given for 8 weeks. The effect characteristics of SQP and ALS in the treatment of SONFH were evaluated by micro-computed tomography scanning， hematoxylin and eosin staining， alkaline phosphatase （ALP） staining， immunohistochemical staining， enzyme-linked immunosorbent assay， and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling（TUNEL）staining， and a comparative efficacy analysis was conducted with ALS. In addition， SONFH cell models were prepared by dexamethasone stimulation of osteoblasts， and the intervention was carried out with the medicated serum of SQP at the aforementioned three doses. Cell counting kit-8， ALP staining， ALP activity assay， alizarin red staining， and flow cytometry were employed to investigate the regulatory effect of SQP on osteoblasts. The expression levels of osteogenesis-related proteins and key factors of the target signaling axis were detected by quantitative real-time polymerase chain reaction and Western blot. ResultsThe network analysis results demonstrated that the candidate targets of SQP primarily exerted their therapeutic effects through key signaling pathways， including phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt）， lipid metabolism and atherosclerosis， prolactin， chemokines， and neurotrophic factors pathways. These pathways were significantly involved in critical biological processes such as muscle and bone metabolism and the regulation of the "neuro-endocrine-immune" network， thereby addressing both modern medical symptoms （e.g.， delayed skeletal maturation and recurrent fractures） and traditional Chinese medicine （TCM） symptoms （e.g.， fatigue， aversion to cold， cold limbs， and pain in the limbs and joints in patients with SONFH characterized by liver and kidney deficiency syndrome. Among these pathways， the PI3K/Akt signaling pathway exhibited the highest degree of enrichment. The in vivo experimental results demonstrated that starting from the 4^th week after modeling， the modeling group exhibited a significant reduction in body weight compared to the control group （P<0.05）. After six weeks of treatment， all dosage groups of SQP showed significantly higher body weights compared to the model group （P<0.01）. Compared with the normal group， the model group exhibited significant decreases in bone mineral density （BMD）， bone volume fraction （BV/TV）， trabecular number （Tb.N）， osteocalcin （OCN）， alkaline phosphatase （ALP） levels in femoral head tissue， and serum bone-specific alkaline phosphatase （BALP） （P<0.01）， along with significant increases in trabecular separation （Tb.Sp）， empty lacunae rate in tissue， and apoptosis rate （P<0.01）. In comparison to the model group， the SQP intervention groups showed significant improvements in BMD， BV/TV and Tb.N （P<0.01）， significant reductions in Tb.Sp， empty lacunae rate and apoptosis rate （P<0.05）， and significant increases in protein levels of OCN and ALP as well as BALP content （P<0.05）. The in vitro experimental results revealed that all dosage groups of SQP medicated serum showed no toxic effects on osteoblast. Compared with the normal group， the model group displayed significant suppression of osteoblast proliferation activity， ALP activity， and calcified nodule formation rate （P<0.01）， significant decreases in mRNA transcription levels of OCN and Runt-related transcription factor 2 （RUNX2） （P<0.01）， significant reductions in protein content of osteopontin （OPN）， typeⅠ collagen （ColⅠ）A1， B-cell lymphoma-2 （Bcl-2）， PI3K， and phosphorylated （p）-Akt （P<0.01）， and a significant increase in apoptosis rate （P<0.01）. Compared with the model group， the SQP medicated serum intervention groups exhibited significant increases in proliferation activity， ALP activity， calcified nodule formation rate， mRNA transcription levels of OCN and RUNX2， and protein content of OPN， ColⅠA1， Bcl-2， PI3K， and p-Akt （P<0.05）， along with a significant decrease in apoptosis rate （P<0.01）. ConclusionSQP can effectively reduce the disease severity of SONFH with liver and kidney deficiency syndrome and improve bone microstructure， with the therapeutic effects exhibiting a dose-dependent manner. The mechanism may be related to its regulation of key processes such as muscle and bone metabolism and the correction of imbalances in the "neuro-endocrine-immune" network， thereby promoting osteoblast differentiation and inhibiting osteoblast apoptosis. The PI3K/Akt signaling axis is likely one of the key pathways through which this formula exerts its effects.

Objective To explore the value of MR modulated flip angle technique in refocused imaging with extended echo train(MATRIX)contrast enhanced(CE)T1-weighted fluid attenuated inversion recovery(T1 FLAIR)for detecting skull metastases.Methods Forty-four patients with malignant tumors who underwent head MR scanning for screening skull metastasis were prospectively enrolled,and skull metastasis were then confirmed by pathology or imaging examinations,including MRI,CT,radionuclide bone imaging(BS),PET/CT and follow-up.Head MATRIX CE-T1 FLAIR(group A),3D gradient recalled echo_fast spin echo with magnetization preparation(GRE_fsp)CE-T1 FLAIR(group B)and fast spin echo(FSE)CE-T1 FLAIR(group C)images of all 44 cases were acquired.The subjective scores(including images quality and diagnostic confidence)and objective evaluation results of images were compared among groups.Taken BS or PET/CT results as standards,the efficacy of 3 kinds of images for detecting skull metastases was calculated.Results The subjective scores of images quality and diagnostic confidence,as well as signal-to-noise ratio(SNR)in group A and C were all higher than those in group B(all P＜0.001),and signal intensity(SI)metastases in group A was higher than those in group B and C(both P＜0.05).No significant difference of subjective score and SNR was found between groups A and C,nor of SImetastases between groups B and C(all P＞0.05).Totally 102 skull metastases were diagnosed with PET/CT or BS,while 129,151 and 115 lesions were detected in group A,B and C,respectively,with accuracy rate of 79.07%(102/129),67.55%(102/151)and 88.70%(102/115),respectively.Conclusion MATRIX CE-T1 FLAIR sequence could be used to detect skull metastases.

Objective To explore the value of MR modulated flip angle technique in refocused imaging with extended echo train(MATRIX)contrast enhanced(CE)T1-weighted fluid attenuated inversion recovery(T1 FLAIR)for detecting skull metastases.Methods Forty-four patients with malignant tumors who underwent head MR scanning for screening skull metastasis were prospectively enrolled,and skull metastasis were then confirmed by pathology or imaging examinations,including MRI,CT,radionuclide bone imaging(BS),PET/CT and follow-up.Head MATRIX CE-T1 FLAIR(group A),3D gradient recalled echo_fast spin echo with magnetization preparation(GRE_fsp)CE-T1 FLAIR(group B)and fast spin echo(FSE)CE-T1 FLAIR(group C)images of all 44 cases were acquired.The subjective scores(including images quality and diagnostic confidence)and objective evaluation results of images were compared among groups.Taken BS or PET/CT results as standards,the efficacy of 3 kinds of images for detecting skull metastases was calculated.Results The subjective scores of images quality and diagnostic confidence,as well as signal-to-noise ratio(SNR)in group A and C were all higher than those in group B(all P＜0.001),and signal intensity(SI)metastases in group A was higher than those in group B and C(both P＜0.05).No significant difference of subjective score and SNR was found between groups A and C,nor of SImetastases between groups B and C(all P＞0.05).Totally 102 skull metastases were diagnosed with PET/CT or BS,while 129,151 and 115 lesions were detected in group A,B and C,respectively,with accuracy rate of 79.07%(102/129),67.55%(102/151)and 88.70%(102/115),respectively.Conclusion MATRIX CE-T1 FLAIR sequence could be used to detect skull metastases.

The discussion on the connotation of children’s subjectivity is not only a response to the lack of children’s subjectivity at the current stage of health management, but also a reference for children’s medical science popularization. Based on the perspective of social critical theory, this study used empirical research methods to review the "Dream Medical College" project of Children’s Hospital of Fudan University. The current situation and influencing factors of health management experience of 1 520 children participating in the "Dream Medical College" project were analyzed. The study showed that 96.35% of 1 316 subjects had diagnosis and treatment experience in specialized hospitals, and the overall negative emotional performance was at a low level (0~12 points). There was significant correlation between diagnosis and treatment, invasive experience and children’s emotional performance (P<0.05). The study revealed that the diagnosis and treatment field is the main practice place of children’s health management, while the subjective of children with different diagnosis and experience perform significantly different. Children over 4 years old have better language anxiety than physical anxiety when receiving diagnosis and treatment. Although medical science popularization is an important practical form of children’s health management, it lacks the science popularization content of invasive diagnosis and treatment and emotional management, and creative popular science form is more suitable for children with long-term and frequent diagnosis and treatment experience.

OBJECTIVE: To identify the protective effect of empagliflozin on ischemic brain injury and neurological dysfunction in mice, and further explore its potential mechanism. METHODS: Acute cerebral ischemia model was induced by the permanent middle cerebral artery occlusion surgery in C57BL/6J mice. Empagliflozin(10 and 30 mg·kg−1) was administered to mice one hour after the onset of occlusion. Brain infarct volume and neurological defect score were assayed 24 h after surgery. Mice were subjected to photo-thrombosis and further administered with empagliflozin 3, 10, 30 mg·kg−1 intragastricly for either 7 or 14 consecutive days. The grid-walking task and the cylinder task were performed daily to determine the sensory-motor function of the mice. Alternatively, the mice were treated with 10 mg·kg−1 empagliflozin simultaneously with 10% glucose(i.p.) for 7 consecutive days after the photo-thrombosis model to evaluate their motor sensory function. Immunofluorescence staining was used to detect the activation of microglia within the infarct area 7 d after the photo-thrombosis. RESULTS: One hour after permanent middle cerebral artery occlusion surgery, gavage of empagliflozin significantly increased the brain infarct volume and neurological dysfunction. While in photo-thrombosis surgery, treatment of empagliflozin(10 mg·kg−1) for consecutive 7 or 14 days significantly decreased the rate of false foot in grid-walking task and the assymetric index in cylinder task. At the dose of 30 mg·kg−1, however, empagliflozin even aggravated photo-thrombosis-induced neurological dysfunction, while the dose of 3 mg·kg−1 showed no effect. Unexpectedly, the protective effect of empagliflozin(10 mg·kg−1) could not be reversed by glucose treatment. The results of immunofluorescence showed that empagliflozin(10 mg·kg−1) significantly alleviated the microglia activation in the ischemic area after the photo-thrombosis operation. CONCLUSION Empagliflozin cannot protect against acute ischemia-induced brain injury in mice. Empagliflozin alleviated ischemia-induced neurological dysfunction with consecutive administration in a dose-related manner. Empagliflozin-conferred neuroprotection may not be attributable to its effects on lowing blood glucose. Alternatively, empagliflozin may play a neuroprotective effect by inhibiting the excessive activation of microglia in ischemic brains.

Objective This study systematically evaluated the clinical efficacy of Shangke Jiegu tablet in the treatment of fracture,and explored the mechanism of action of Shangke Jiegu tablet and the compatibility of each efficacy group from the"Disease-Symptom-Formula"perspective.Methods Clinical research literatures on the use of Shangke Jiegu tablet for fracture intervention were retrieved from Chinese databases(CNKI,Wanfang Database,VIP database)and English databases(PubMed,Cochrane Library,EMbase),covering the period from the inception of the databases to January 2024.Risk assessment tools were used to evaluate the literature's quality,and the data were extracted and analyzed using Stata 16.0 software.Gene sets associated with fracture symptoms were identified through the TCMIP platform(version 2.0).Differential gene expression related to fractures was obtained from the GEO database.Chemical composition and candidate target profiles of the 12 herbs in Shangke Jiegu tablets were collected from TCMIP v 2.0.An interaction network between fracture-related genes and drug candidate targets was established,and core network targets were screened based on topological features,with functional enrichment analysis performed.Results A total of 14 articles were incorporated into the Meta-analysis,encompassing a total sample size of 1 293 cases,indicating an overall response rate of Shangke Jiegu tablets in fracture therapy(RR=1.24,95%CI:1.18-1.31,P<0.001).The"Disease-Symptom-Formula"association network analysis indicated that the pathways related to the putative targets of Shangke Jiegu tablet were primarily involved in bone healing,nerve and blood system regulation,and immune-inflammation regulation.Different efficacy groups within the prescriptions showed varying emphases on these roles.Conclusions Shangke Jiegu tablet may facilitate fracture healing by regulating blood and nervous systems,correcting immune-inflammatory imbalances,and maintaining bone and energy metabolism.The comprehensive effects include the dissipation of blood stasis,the promotion of blood circulation,the alleviation of swelling and pain,the regeneration of muscles and bones,and the clearance of heat and detoxification.These findings support the clinical advantages and positioning of Shangke Jiegu tablet.

ObjectiveFrom the perspective of energy metabolism， the mechanism of Osteoking （OK） in the treatment of myofascial pain syndrome （MPS） was revealed through systems biology prediction combined with holistic animal experimental validation methods. MethodFirstly， the key targets of MPS and their related molecular mechanisms were predicted by the systems biology method， and the core network targets were screened. Then， the network-predicted targets were verified by animal experiments. Specifically， 60 SD rats were randomly divided into normal group， model group， low， medium， and high dose OK groups （0.66， 1.31， 2.63 mL·kg^-1）， and positive celecoxib group （21 mg·kg^-1）. The MPS model was established by beating combined with a centrifugal exercise method for eight weeks. Except for two days after modeling， the intervention of OK or celecoxib was performed. After the completion of the model， the drug was administered for two weeks. The histopathological changes of trigger point muscle tissue were observed by hematoxylin-eosin staining. The content/activity of Na-K-ATP enzyme （Na⁺-K⁺-ATPase）， Ca²⁺ pump （Ca²⁺ATPase）， Ca²⁺， lactate dehydrogenase （LDH）， glutathione （GSH）， malondialal （MDA）， superoxide dismutase （SOD）， cyclic adenosine phosphate （cAMP）， and protein kinase A （PKA） in serum and/or trigger point muscle tissue in MPS rats was detected by enzyme-linked immunosorbent assay. Protein expression levels of PKA and the peroxisome proliferator-activated receptor γ coactivator 1α （PGC1α） in MPS rats were detected by immunohistochemistry. The protein expression levels of PKA， PGC1α， and mitochondrial transcription factor A （TFAM） in MPS rats were detected by Western blot. ResultThe network prediction results suggest that OK acts on the key target of energy metabolism related to the occurrence and development of MPS and may participate in the activation of the cAMP/PKA/PGC1α signaling pathway. The experimental validation results show that compared with the normal group， contracture nodules and disordered arrangement of muscle fibers appear in the trigger point muscle tissue of MPS rats. Na⁺-K⁺-ATPase， Ca²⁺ATPase， SOD activity， Ca²⁺， and GSH contents in serum and/or trigger point muscle tissue are significantly decreased （P<0.01）. Both LDH activity and MDA contents are significantly increased （P<0.01）， and the protein expression levels of cAMP， PKA， PGC1α， and TFAM are significantly decreased （P<0.01）. Compared with the model group， OK improves the histopathological morphology of trigger point muscle fibers in MPS rats， and after the intervention of OK， Na⁺-K⁺-ATPase， Ca²⁺ATPase， SOD activity， Ca²⁺， and GSH contents in serum and/or trigger point muscle tissue in MPS rats are significantly increased （P<0.05， P<0.01）. LDH activity and MDA contents are significantly reduced （P<0.05， P<0.01）. The protein expression levels of cAMP， PKA， PGC1α， and TFAM are significantly increased （P<0.05， P<0.01）. ConclusionThe mechanism of OK's intervention in MPS rats may be related to its effective activation of the cAMP/PKA/PGC1α signaling pathway， thus promoting mitochondrial energy metabolism and trigger point muscle fiber damage repair in muscle cells.

The discussion on the connotation of children’s subjectivity is not only a response to the lack of children’s subjectivity at the current stage of health management, but also a reference for children’s medical science popularization. Based on the perspective of social critical theory, this study used empirical research methods to review the "Dream Medical College" project of Children’s Hospital of Fudan University. The current situation and influencing factors of health management experience of 1 520 children participating in the "Dream Medical College" project were analyzed. The study showed that 96.35% of 1 316 subjects had diagnosis and treatment experience in specialized hospitals, and the overall negative emotional performance was at a low level (0~12 points). There was significant correlation between diagnosis and treatment, invasive experience and children’s emotional performance (P<0.05). The study revealed that the diagnosis and treatment field is the main practice place of children’s health management, while the subjective of children with different diagnosis and experience perform significantly different. Children over 4 years old have better language anxiety than physical anxiety when receiving diagnosis and treatment. Although medical science popularization is an important practical form of children’s health management, it lacks the science popularization content of invasive diagnosis and treatment and emotional management, and creative popular science form is more suitable for children with long-term and frequent diagnosis and treatment experience.

Hepatocellular carcinoma (HCC) is a common malignant tumor and patients with HCC often have liver cirrhosis, with an extremely high 5-year recurrence rate and poor prognosis even after curative treatment. In recent years, sarcopenia has attracted more and more attention as a poor prognostic factor for various malignant tumors; however, there is still a lack of studies on the association between skeletal muscle index and prognosis of HCC in China. Evidence in foreign countries has shown that sarcopenia may be an a negative prognostic factor for HCC patients. This article reviews the etiology and possible pathogenesis of HCC-related sarcopenia and related intervention measures including nutritional supplementation, appropriate physical exercise, and medication, in order to provide a reference for related studies in China.

Objective To explore the effect of age factor on the degree of pulmonary fibrosis and on the change in telomerase reverse transcriptase(TERT) activity in mice.Methods A total of 80 healthy male C57BL/6 mice aged 20-weeks were randomized into 4 groups:a young pulmonary fibrosis model group(n=20),a young control group(n=20),a senile pulmonary fibrosis model group(n=20),and an elderly control group (n =20).Two model groups were induced by an intratracheally injected bleomycin in 5 mg/kg,and two control groups by an intratracheally injected normal saline.The elderly were defined as 26 weeks old mice.Five mouse pulmonary fibrosis models and five mouse controls in four groups were randomly selected and killed at 7,14,21,28 days.Lung tissue specimens were stained with hematoxylin eosin (HE)and Masson trichrome (Masson)method,and then pathological changes were observed.In addition,immunohisto-chemical staining was used to observe the expression levels of epithelial cell marker protein E-cadherin(E-cad),stromal cell marker protein Vimentin,and alpha smooth muscle actin(α-SMA).Finally,the expression level of telomerase reverse transcriptase(TERT)protein was detected by Western blotting.Results A bleomycin-induced pulmonary fibrosis mice model was successfully prepared.The degree of pulmonary fibrosis was more severe in old mice than in young mice.Compared with the young pulmonary fibrosis model group,the expression level of E-Cad was decreased in the senile pulmonary fibrosis model group(P ＜0.05).Compared with the young control group and the elderly control group,the expression levels of E-Cad in the young pulmonary fibrosis model group and the senile pulmonary fibrosis model group were decreased (P ＜ 0.05),and decreased along with the prolongation of the modeling time.Compared with the young pulmonary fibrosis model group,the expression levels of alpha-SMA and vimentin were increased in the senile pulmonary fibrosis model group(P ＜ 0.05).The expression levels of alpha-SMA and vimentin were increased in the young pulmonary fibrosis model group and the senile pulmonary fibrosis model group,as compared to the young control group and the elderly control group(P＜0.05),and increased along with the prolongation of the modeling time.The activity of TERT in lung tissue of mice was increased at first and then decreased.Compared with the young pulmonary fibrosis model group,the activity of TERT in the senile pulmonary fibrosis model group significantly fluctuated(P＜0.05).Conclusions Age factor can affect the severity of pulmonary fibrosis by affecting the activity of telomerase reverse transcriptase in mouse models of pulmonary fibrosis.