ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

ObjectiveTo measure the distance from the surface of Fengfu （GV 16） to the deep important bony structures in children aged 4 to 8 years based on CT three-dimensional reconstruction technology， thereby providing imaging reference data for clinical acupuncture safe operations in terms of different age groups and needle insertion angles. MethodsCervical CT image data were collected from healthy children aged 4 to 8 years with five age groups （4-， 5-， 6-， 7-， 8-year-old groups）， 20 cases in each group. The images were imported into Mimics 21.0 software for three-dimensional reconstruction. The straight-line distances from the skin model surface of the Fengfu （GV 16） to the first underlying bony barrier （such as the lower edge of the occipital bone， the posterior arch of the atlas vertebra） were measured at intervals of 5° on both the transverse section （0° ± 35°） and the sagittal section （40° upward to 40° downward on the diagonal）. The correlation between the measured distance， age， and angle was analyzed. ResultsIn the transverse and sagittal sections， the measured distance from the skin surface to the underlying bone of Fengfu （GV 16） at each angle increased with age. In the transverse section， the increase was relatively small within the 0° to 20° angle range， whereas a more pronounced increase was observed when the angle exceeded 20°； at measurement angles of 30° to 35°， the distance of the skin surface to the bone at Fengfu （GV 16） in the 7- and 8-year-old groups was significantly greater than that in the 4-year-old group （P＜0.05）. In the sagittal section， the measured distance from the skin surface to the bone at Fengfu （GV 16） was shortest and changed greatly at oblique upward angles of 15° to 40° within each age group， and increased markedly at near-vertical angles of 0° to 10°； it was longest at oblique downward angles of -40° to -5° and showed relatively gradual changes. ConclusionThis study obtained the imaging distance data from Fengfu （GV 16） to the surrounding bony structures in children aged 4 to 8 years through three-dimensional modeling， finding that this distance has clear age and angle dependence， which can provide quantitative evidence for developing individualized and precise safe acupuncture schemes at Fengfu （GV 16） in pediatric clinical practice.

ObjectiveTo measure the distance from the surface of Fengfu （GV 16） to the deep important bony structures in children aged 4 to 8 years based on CT three-dimensional reconstruction technology， thereby providing imaging reference data for clinical acupuncture safe operations in terms of different age groups and needle insertion angles. MethodsCervical CT image data were collected from healthy children aged 4 to 8 years with five age groups （4-， 5-， 6-， 7-， 8-year-old groups）， 20 cases in each group. The images were imported into Mimics 21.0 software for three-dimensional reconstruction. The straight-line distances from the skin model surface of the Fengfu （GV 16） to the first underlying bony barrier （such as the lower edge of the occipital bone， the posterior arch of the atlas vertebra） were measured at intervals of 5° on both the transverse section （0° ± 35°） and the sagittal section （40° upward to 40° downward on the diagonal）. The correlation between the measured distance， age， and angle was analyzed. ResultsIn the transverse and sagittal sections， the measured distance from the skin surface to the underlying bone of Fengfu （GV 16） at each angle increased with age. In the transverse section， the increase was relatively small within the 0° to 20° angle range， whereas a more pronounced increase was observed when the angle exceeded 20°； at measurement angles of 30° to 35°， the distance of the skin surface to the bone at Fengfu （GV 16） in the 7- and 8-year-old groups was significantly greater than that in the 4-year-old group （P＜0.05）. In the sagittal section， the measured distance from the skin surface to the bone at Fengfu （GV 16） was shortest and changed greatly at oblique upward angles of 15° to 40° within each age group， and increased markedly at near-vertical angles of 0° to 10°； it was longest at oblique downward angles of -40° to -5° and showed relatively gradual changes. ConclusionThis study obtained the imaging distance data from Fengfu （GV 16） to the surrounding bony structures in children aged 4 to 8 years through three-dimensional modeling， finding that this distance has clear age and angle dependence， which can provide quantitative evidence for developing individualized and precise safe acupuncture schemes at Fengfu （GV 16） in pediatric clinical practice.

Objective To investigate the clinical efficacy and safety of sintilimab combined with gemcitabine hydrochloride plus cisplatin in treating patients with advanced lung squamous cell carcinoma(LSCC).Methods A total of 102 patients with advanced LSCC who were admitted to our hospital between November 2020 and January 2024 were enrolled and randomly assigned to control group(n=51,treated with gemcitabine hydrochloride plus cisplatin)or sintilimab group(n=51,treated with sintilimab,gemcitabine hydrochloride and cisplatin).Clinical efficacy,tumor markers,immune function,quality of life,survival outcomes,and safety were compared between the two groups.Results The objective response rate(ORR)in the sintilimab group was significantly higher than that in the control group(60.78%vs.39.22%,P<0.05).Serum levels of squamous cell carcinoma antigen(SCCAg),carcinoembryonic antigen(CEA),and cytokeratin 19 fragment(CYFRA 21-1)in the sintilimab group were significantly lower than those in the control group after treatment(P<0.05).The sintilimab group had higher CD4+T-cell levels and CD4+/CD8+ratio and lower CD8+T-cell levels than the control group after treatment(P<0.05).The Karnofsky Performance Status(KPS)score was significantly improved in the sintilimab group compared to the control group(P<0.05).Median progression-free survival(PFS)and overall survival(OS)in the sintilimab group were significantly higher than those in the control group(both P<0.05).No significant difference in adverse event rates was observed between the two groups(P>0.05).Conclusion Sintilimab combined with gemcitabine hydrochloride and cisplatin can significantly increase tumor control rates and immune function,prolong survival,improve quality of life,and demonstrate favorable safety in advanced LSCC patients.

Objective: To explore the clinical characteristics of transfusion-associated graft-versus-host disease (TA-GVHD) in Chinese population, and to provide reference for effective prevention. Methods: Chinese and English medical databases were searched, and literature was screened based on inclusion and exclusion criteria. Data on patient information, clinical manifestations, outcomes and related risk factors from the selected studies were summarized and systematically analyzed. Results: A total of 17 studies were included in this study, involving 55 non-duplicated patients [14 males (14/55, 25.45%) and 41 females (41/55, 74.55%)], with a mean age of 51.72±18.34 years, (range: 2 months to 82 years). Among these cases, 2 had congenital immune deficiency (2/55, 3.64%), 16 had malignant hematological diseases (16/55, 29.09%), 4 had a history of surgery or trauma (4/55, 7.27%), 2 received non-surgical treatment (2/55, 3.64%), 31 were critically ill patients (31/55, 56.36%). Whole blood was transfused in 3 cases (3/55, 5.45%), erythrocyte in 9 (9/55, 16.36%), plasma in 2 (2/55, 3.64%), platelets in 7(7/55, 12.73%), human fibrinogen in 1 (1/55, 1.82%), and granulocytes in 2 (2/55, 3.64%). Two or more types of blood components were transfused in 16 cases (16/55, 29.09%). The main clinical signs and symptoms included fever (23/55, 41.82%), rash (22/55, 40.00%), diarrhea (14/55, 25.45%), abnormal liver function (18/55, 32.73%), bone marrow suppression and pancytopenia (22/55, 40.00%). The survival rate of 55 patients was 43.64% (24/55), and the mortality was 56.36% (31/55). Logistic regression analysis suggested that gender, misdiagnosis or missed diagnosis were major risk factors for mortality in TA-GVHD patients. Conclusion: The lack of specific indications for TA-GVHD often causes clinical misdiagnosis and missed diagnosis, and current treatments have limited efficacy. Therefore, it is of great significance to standardize clinical diagnosis criteria and improve prevention techniques to reduce the risk and mortality rate of TA-GVHD.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

Steroid-induced osteonecrosis of femoral head (SONFH) is a disease characterized by femoral head collapse and local pain caused by excessive use of glucocorticoids. Peroxisome proliferator-activated receptor-γ (PPARγ) is mainly expressed in adipose tissue. Wnt/β-catenin, AMPK and other related signaling pathways play an important role in regulating adipocyte differentiation, fatty acid uptake and storage. Bone marrow mesenchymal cells (BMSCs) have the ability to differentiate into adipocytes or osteoblasts, and the use of hormones upregulates PPARγ expression, resulting in BMSCs biased towards adipogenic differentiation. The increase of adipocytes affects the blood supply and metabolism of the femoral head, and the decrease of osteoblasts leads to the loss of trabecular bone, which eventually leads to partial or total ischemic necrosis and collapse of the femoral head. MicroRNAs (miRNAs) are a class of short non-coding RNAs that regulate gene expression by inhibiting the transcription or translation of target genes, thereby affecting cell function and disease progression. Studies have shown that miRNAs affect the progression of SONFH by regulating PPARγ lipid metabolism-related signaling pathways. Therefore, it may be an accurate and feasible SONFH treatment strategy to regulate adipogenic-osteoblast differentiation in BMSCs by targeted intervention of miRNA differential expression to improve lipid metabolism. In this paper, the miRNA-mediated PPARγ-related signaling pathways were classified and summarized to clarify their effects on lipid metabolism in SONFH, providing a theoretical reference for miRNA targeted therapy of SONFH, and then providing scientific evidence for SONFH precision medicine.
MicroRNAs/physiology* ; PPAR gamma/metabolism* ; Femur Head Necrosis/metabolism* ; Humans ; Signal Transduction/physiology* ; Lipid Metabolism/physiology* ; Animals ; Cell Differentiation ; Mesenchymal Stem Cells/cytology* ; Glucocorticoids/adverse effects*

In this experiment, self-assembled nanoparticles(SANs) were prepared by the pH-driven method, and Her-HCP SAN was constructed by using herpetrione(Her) and Herpetospermum caudigerum polysaccharides(HCPs). The average particle size and polydispersity index(PDI) were used as evaluation indexes for process optimization, and the quality of the final formulation was evaluated in terms of particle size, PDI, Zeta potential, and microstructure. The proposed Her-HCP SAN showed a spheroid structure and uniform morphology, with an average particle size of(244.58±16.84) nm, a PDI of 0.147 1±0.014 8, and a Zeta potential of(-38.52±2.11) mV. Her-HCP SAN significantly increased the saturation solubility of Her by 2.69 times, with a cumulative release of 90.18% within eight hours. The results of in vivo unidirectional intestinal perfusion reveal that Her active pharmaceutical ingredient(API) is most effectively absorbed in the jejunum, where both K_a and P_(app) are significantly higher compared to the ileum(P<0.001). However, the addition of HCP leads to a significant reduction in the P_(app) of Her in the jejunum(P<0.05). Furthermore, the formation of the Her-HCP SAN results in a notably lower P_(app) in the jejunum compared to Her API alone(P<0.001), while both K_a and P_(app) in the ileum are significantly increased(P<0.001, P<0.05). The absorption of Her-HCP SAN at different concentrations in the ileum shows no significant differences, and the pH has no significant effect on the absorption of Her-HCP SAN in the ileum. The addition of the transporter protein inhibitors(indomethacin and rifampicin) significantly increases the absorption parameters K_a and P_(app) of Her-HCP SAN in the ileum(P<0.05,P<0.01), whereas the addition of verapamil has no significant effect on the intestinal absorption parameters of Her-HCP SAN, suggesting that Her may be a substrate for multidrug resistance-associated protein 2 and breast cancer resistance proteins but not a substrate of P-glycoprotein.
Nanoparticles/metabolism* ; Polysaccharides/pharmacokinetics* ; Intestinal Absorption/drug effects* ; Animals ; Rats ; Particle Size ; Drugs, Chinese Herbal/pharmacokinetics* ; Male ; Rats, Sprague-Dawley ; Drug Carriers/chemistry* ; Drug Compounding ; Cucurbitaceae/chemistry*

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

Heart failure is a complex clinical syndrome and pediatric heart failure (PHF) has a high mortality rate. Early diagnosis is crucial for treatment and management of PHF. In clinical practice, various tests and examinations play a key role in the diagnosis of PHF, including continuously updated biomarkers, echocardiography, and cardiac magnetic resonance imaging. This article focuses on summarizing relevant research on biomarkers, examinations, combined testing, clinical models, and the grading and staging of PHF diagnosis, aiming to provide insights and directions for the diagnosis of PHF.
Humans ; Heart Failure/diagnosis* ; Child ; Biomarkers/blood* ; Echocardiography ; Magnetic Resonance Imaging