Background: Bushen Zhuanggu Formula (BZF), derived from the classic Yougui Pills, has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head (NONFH), particularly by promoting bone repair. However, its underlying mechanisms remain unclear. Objective: This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH. Materials and methods: A total of 518 potential BZF targets were identified from the ETCM v2.0 database. Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls. A drug target-disease gene interaction network was constructed to identify candidate BZF targets involved in NONFH pathogenesis. In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH. Results: Network analysis identified key pathways associated with blood circulation obstruction, immune-inflammatory imbalance, and abnormal bone metabolism. Protein kinase C alpha (PKCA), Ras proto-oncogene (RAS), mitogen-activated protein kinase 3(ERK), ETS proto-oncogene 1 (ETS1), and receptor activator of nuclear factor-κB ligand (RANKL) formed a signaling axis implicated in NONFH pathogenesis. BZF treatment alleviated joint inflammation, preserved trabecular bone morphology, reduced bone loss, and promoted bone repair. Mechanistically, BZF significantly downregulated the expression of PKCA, RAS, ERK, ETS1, and RANKL, improved blood circulation, and inhibited osteoclast activation while promoting osteoblast activation. Conclusion: BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis, thereby reversing dysregulated bone metabolism.

The patient is a male neonate born at term. He was admitted 16 minutes after birth due to stridor and inspiratory respiratory distress. Physical examination revealed a cleft palate, and a grade II systolic ejection murmur was audible at the left sternal border. Whole exome sequencing identified a heterozygous variant in the SON gene, c.5753-5756del (p.Val1918GlufsTer87), which was absent in either parent, indicating a de novo mutation. According to the guidelines of the American College of Medical Genetics and Genomics, this was classified as a "pathogenic variant" leading to a diagnosis of Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome. Upon admission, symptomatic supportive treatment was provided. Follow-up at the age of 8 months revealed persistent stridor; the infant could only consume small amounts of milk and was unable to sit steadily. This patient represents the youngest reported case to date, and his symptoms expand the clinical spectrum of the disease, providing valuable insights for clinical diagnosis and treatment.
Humans ; Infant, Newborn ; Male ; Minor Histocompatibility Antigens/genetics* ; DNA-Binding Proteins/genetics* ; Rare Diseases/genetics* ; Neurodevelopmental Disorders/genetics*

Objective:To investigate the association of systemic immune-inflammation index(SII)and serum cysta-tin C(CysC)with the severity of acute pulmonary embolism(APE),and their predictive value for prognosis.Meth-ods:A total of 181 patients who were first diagnosed with APE in Cangzhou People's Hospital between January 2018 and January 2023 were retrospectively selected.The severity of APE was determined according to risk stratification criteria for pulmonary embolism,and the patients were divided into low-risk group(n=67),middle-risk group(n=81)and high-risk group(n=33).General clinical data and venous blood neutrophils,platelet and lymphocyte counts,CysC and other indicators were collected,and SII was calculated according to the formula.The relevant in-dicators were compared among three groups,and their correlation with the severity of APE was analyzed by Spearman correlation analysis.According to the prognosis,all APE patients were divided into favorable outcome group(n=129)and unfavorable outcome group(n=52).The general clinical data were compared and multivariate Cox regression analysis was used to study the influencing factors of unfavorable outcome in APE patients.The re-ceiver operating characteristic curve(ROC)was drawn to evaluate the predictive value of SII,CysC and their com-bination for the prognosis of APE patients.Nomogram model for prognosis was constructed.Results:Compared with patients in low-risk group,those in the middle-risk group and the high-risk group had significantly higher levels of serum creatinine,CysC and uric acid(P＜0.05 or＜0.01).The SII in the high-risk group was significant-ly higher than those of middle-risk group and low-risk group(P＜0.001 all).Spearman correlation analysis showed that serum creatinine,CysC,uric acid and SII were significant positively correlated with the severity of APE(r=0.356,0.358,0.233,0.353,P＜0.01 all).Compared with patients in the favorable outcome group,those in the unfavorable outcome group had significantly higher levels of D-dimer,serum creatinine,CysC,uric acid and SII(P＜0.01 all).There was a statistically significant difference in the severity of APE between the two groups(P=0.001).Multivariate Cox regression analysis showed that CysC,SII,and middle or high risk of disease severity were independent risk factors for unfavorable outcome in APE patients(HR=1.001～14.453,P＜0.05 or＜0.01).ROC curve indicated that the AUC of SII,CysC and their combination in predicting unfavorable outcome of APE patients were 0.815(95％CI 0.749～0.881),0.747(95％CI 0.661～0.832)and 0.878(95％CI,0.821～0.936),respectively.The combined AUC of the two was significantly higher than those of SII and CysC alone(Z=-2.234,-3.500,P＜0.05 or＜0.01).Based on the above independent risk factors,the AUC values of the 1-year and 3-year unfavorable outcome nomogram models were 92.9 and 88.2,respectively.The calibration prediction curve and the ideal curve fitted well.The decision curve showed that the model had a good net benefit.Conclusion:SII and CysC are significant positively correlated with the severity of APE and they are independent risk factors for unfavor-able outcome of APE,and the combination of the two indicators has a good predictive value for the prognosis of APE.The nomogram constructed has good accuracy and practicability.

Background:Bushen Zhuanggu Formula(BZF),derived from the classic Yougui Pills,has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head(NONFH),particularly by promoting bone repair.However,its underlying mechanisms remain unclear.Objective:This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH.Materials and methods:A total of 518 potential BZF targets were identified from the ETCM v2.0 database.Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls.A drug target-disease gene interaction network was constructed to identify candidate BZF targets involved in NONFH pathogenesis.In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH.Results:Network analysis identified key pathways associated with blood circulation obstruction,immune-inflammatory imbalance,and abnormal bone metabolism.Protein kinase C alpha(PKCA),Ras proto-oncogene(RAS),mitogen-activated protein kinase 3(ERK),ETS proto-oncogene 1(ETS1),and receptor activator of nuclear factor-κB ligand(RANKL)formed a signaling axis implicated in NONFH pathogenesis.BZF treatment alleviated joint inflammation,preserved trabecular bone morphology,reduced bone loss,and promoted bone repair.Mechanistically,BZF significantly downregulated the expression of PKCA,RAS,ERK,ETS1,and RANKL,improved blood circulation,and inhibited osteoclast activation while promoting osteoblast activation.Conclusion:BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis,thereby reversing dysregulated bone metabolism.

Objective:To investigate the clinical features and multi-slice spiral computed tomography(CT)imaging features of acute appendicitis in soldiers who have been living in plateau for a long time.Methods:The clinical features and imaging data of 56 cases of acute appendicitis in soldiers who have been living in plateau for a long time confirmed by surgery from February 2022 to August 2024 were retrospectively analyzed.Results:In 56 cases with acute appendicitis in soldiers who have been living in plateau for a long time,the appendectomy position results showed:anterior ileum 4 cases(7.14％),lower ileum 10 cases(17.86％),posterior cecum 16 cases(28.57％),lower cecum 9 cases(16.07％),lateral cecum 2 cases(3.58％),posterior ileum 6 cases(10.71％),high(subhepatic)9 cases(16.07％),and left lower abdominal 0 cases,retroperitoneal appendicitis 0 cases,which was suggested that the anatomical position variation of appendicitis in soldiers with acute appendicitis who have been living at high altitude for a long time was relatively large.The direct manifestations of multi-slice spiral CT showed:appendectomy enlarged diameter＞6 mm in 49 cases(87.50％),appendicular wall thickening＞2 mm in 42 cases(75.00％),ppendiceal dilation lumen and effusion in 29 cases(51.79％),appendix indistinctness in 3 cases(5.36％),lppendix fecalith:27 cases(48.21％),gas in the appendix in 16 cases(28.57％).Indirect findings of multi-slice spiral CT showed that,periappendiceal exudation with shadow in 32 cases(57.14％),appendiceal cellulitis with peripheral abscess in 9 cases(16.07％),peritonitis and ascites in 13 cases(23.21％),ileocecal intestinal wall thickening in 22 cases(39.29％),mesenteric lymph node enlargement in 16 cases(28.57％),reflexive intestinal stasis in ileocecal region was observed in 19 cases(33.93％).Conclusion:In the officers and soldiers with acute appendicitis who lived at high altitude for a long time,multi-slice spiral CT showed the direct manifestations of appendiceal thickening,tube wall thickening,lumen dilatation,fluid accumulation,etc.,and the indirect manifestations were periappendiceal exudation with shadow,appendiceal cellulitis with peripheral abscess,ileocecal intestinal wall thickening,reflexes of small intestine and mesenteric lymph node enlargement.Multi-slice spiral CT has the advantages of clear and intuitive,high safety,high resolution and simple operation in the diagnosis of acute appendicitis.

Background:Bushen Zhuanggu Formula(BZF),derived from the classic Yougui Pills,has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head(NONFH),particularly by promoting bone repair.However,its underlying mechanisms remain unclear.Objective:This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH.Materials and methods:A total of 518 potential BZF targets were identified from the ETCM v2.0 database.Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls.A drug target-disease gene interaction network was constructed to identify candidate BZF targets involved in NONFH pathogenesis.In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH.Results:Network analysis identified key pathways associated with blood circulation obstruction,immune-inflammatory imbalance,and abnormal bone metabolism.Protein kinase C alpha(PKCA),Ras proto-oncogene(RAS),mitogen-activated protein kinase 3(ERK),ETS proto-oncogene 1(ETS1),and receptor activator of nuclear factor-κB ligand(RANKL)formed a signaling axis implicated in NONFH pathogenesis.BZF treatment alleviated joint inflammation,preserved trabecular bone morphology,reduced bone loss,and promoted bone repair.Mechanistically,BZF significantly downregulated the expression of PKCA,RAS,ERK,ETS1,and RANKL,improved blood circulation,and inhibited osteoclast activation while promoting osteoblast activation.Conclusion:BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis,thereby reversing dysregulated bone metabolism.

Objective:To investigate the association of systemic immune-inflammation index(SII)and serum cysta-tin C(CysC)with the severity of acute pulmonary embolism(APE),and their predictive value for prognosis.Meth-ods:A total of 181 patients who were first diagnosed with APE in Cangzhou People's Hospital between January 2018 and January 2023 were retrospectively selected.The severity of APE was determined according to risk stratification criteria for pulmonary embolism,and the patients were divided into low-risk group(n=67),middle-risk group(n=81)and high-risk group(n=33).General clinical data and venous blood neutrophils,platelet and lymphocyte counts,CysC and other indicators were collected,and SII was calculated according to the formula.The relevant in-dicators were compared among three groups,and their correlation with the severity of APE was analyzed by Spearman correlation analysis.According to the prognosis,all APE patients were divided into favorable outcome group(n=129)and unfavorable outcome group(n=52).The general clinical data were compared and multivariate Cox regression analysis was used to study the influencing factors of unfavorable outcome in APE patients.The re-ceiver operating characteristic curve(ROC)was drawn to evaluate the predictive value of SII,CysC and their com-bination for the prognosis of APE patients.Nomogram model for prognosis was constructed.Results:Compared with patients in low-risk group,those in the middle-risk group and the high-risk group had significantly higher levels of serum creatinine,CysC and uric acid(P＜0.05 or＜0.01).The SII in the high-risk group was significant-ly higher than those of middle-risk group and low-risk group(P＜0.001 all).Spearman correlation analysis showed that serum creatinine,CysC,uric acid and SII were significant positively correlated with the severity of APE(r=0.356,0.358,0.233,0.353,P＜0.01 all).Compared with patients in the favorable outcome group,those in the unfavorable outcome group had significantly higher levels of D-dimer,serum creatinine,CysC,uric acid and SII(P＜0.01 all).There was a statistically significant difference in the severity of APE between the two groups(P=0.001).Multivariate Cox regression analysis showed that CysC,SII,and middle or high risk of disease severity were independent risk factors for unfavorable outcome in APE patients(HR=1.001～14.453,P＜0.05 or＜0.01).ROC curve indicated that the AUC of SII,CysC and their combination in predicting unfavorable outcome of APE patients were 0.815(95％CI 0.749～0.881),0.747(95％CI 0.661～0.832)and 0.878(95％CI,0.821～0.936),respectively.The combined AUC of the two was significantly higher than those of SII and CysC alone(Z=-2.234,-3.500,P＜0.05 or＜0.01).Based on the above independent risk factors,the AUC values of the 1-year and 3-year unfavorable outcome nomogram models were 92.9 and 88.2,respectively.The calibration prediction curve and the ideal curve fitted well.The decision curve showed that the model had a good net benefit.Conclusion:SII and CysC are significant positively correlated with the severity of APE and they are independent risk factors for unfavor-able outcome of APE,and the combination of the two indicators has a good predictive value for the prognosis of APE.The nomogram constructed has good accuracy and practicability.

Objective:To investigate the clinical features and multi-slice spiral computed tomography(CT)imaging features of acute appendicitis in soldiers who have been living in plateau for a long time.Methods:The clinical features and imaging data of 56 cases of acute appendicitis in soldiers who have been living in plateau for a long time confirmed by surgery from February 2022 to August 2024 were retrospectively analyzed.Results:In 56 cases with acute appendicitis in soldiers who have been living in plateau for a long time,the appendectomy position results showed:anterior ileum 4 cases(7.14％),lower ileum 10 cases(17.86％),posterior cecum 16 cases(28.57％),lower cecum 9 cases(16.07％),lateral cecum 2 cases(3.58％),posterior ileum 6 cases(10.71％),high(subhepatic)9 cases(16.07％),and left lower abdominal 0 cases,retroperitoneal appendicitis 0 cases,which was suggested that the anatomical position variation of appendicitis in soldiers with acute appendicitis who have been living at high altitude for a long time was relatively large.The direct manifestations of multi-slice spiral CT showed:appendectomy enlarged diameter＞6 mm in 49 cases(87.50％),appendicular wall thickening＞2 mm in 42 cases(75.00％),ppendiceal dilation lumen and effusion in 29 cases(51.79％),appendix indistinctness in 3 cases(5.36％),lppendix fecalith:27 cases(48.21％),gas in the appendix in 16 cases(28.57％).Indirect findings of multi-slice spiral CT showed that,periappendiceal exudation with shadow in 32 cases(57.14％),appendiceal cellulitis with peripheral abscess in 9 cases(16.07％),peritonitis and ascites in 13 cases(23.21％),ileocecal intestinal wall thickening in 22 cases(39.29％),mesenteric lymph node enlargement in 16 cases(28.57％),reflexive intestinal stasis in ileocecal region was observed in 19 cases(33.93％).Conclusion:In the officers and soldiers with acute appendicitis who lived at high altitude for a long time,multi-slice spiral CT showed the direct manifestations of appendiceal thickening,tube wall thickening,lumen dilatation,fluid accumulation,etc.,and the indirect manifestations were periappendiceal exudation with shadow,appendiceal cellulitis with peripheral abscess,ileocecal intestinal wall thickening,reflexes of small intestine and mesenteric lymph node enlargement.Multi-slice spiral CT has the advantages of clear and intuitive,high safety,high resolution and simple operation in the diagnosis of acute appendicitis.

Objective To evaluate the effects of high-fat diet on the pharmacokinetics of metronidazole in Chinese healthy adult subjects.Methods This program is designed according to a single-center,randomized,open,single-dose trial.Forty-seven healthy subjects were assigned to receive single dose of metronidazole tablets 200 mg in either fasting and high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of metronidazole in plasma were determined by high performance liquid chromatography-mass spectromentry.Results The main pharmacokinetic parameters of metronidazole in fasting state and high-fat diet state were as follows:Cmax were(4 799.13±1 195.32)and(4 044.17±773.98)ng·mL-1;tmax were 1.00 and 2.25 h;t1/2 were(9.11±1.73)and(9.37±1.79)h;AUC0_t were(5.59±1.19)x 104 and(5.51±1.18)x 104 ng·mL-1·h;AUC0_∞ were(5.79±1.33)x 104 and(5.74±1.32)× 104 ng·mL-1·h.Compared to the fasting state,the tmaxof the drug taken after a high fat diet was delayed by 1.25 h(P＜0.01),Cmax,AUC0_t,AUC0-∞ were less or decreased in different degrees,but the effects were small(all P＞0.05).Conclusion High-fat diet has little effects on the pharmacokinetic parameters of metronidazole,which does not significantly change the degree of drug absorption,but can significantly delay the time to peak.

Objective To investigate the therapeutic effect and mechanism of paeoniflorin(PAE)on thrombosis angiitis obliterans(TAO)in rats.Methods TAO rat model was established by sodium laurate injection.Rats were randomly divided into sham operation group(intraperitoneal injection of 0.9％NaCl),model group(intraperitoneal injection of 0.9％NaCl),experimental-L,-H groups(intraperitoneal injection of PAE 5,20 mg·kg-1·d-1),experimental-H+agonist group(intraperitoneal injection of 20 mg·kg-1·d-1 PAE+caudal vein injection of 10 ng·mL-1·kg 1·d-1 740 Y-P).Thrombin time(TT)was measured by magnetic bead coagulation;the levels of interleukin(IL)-1 β and endothelin 1(ET-1)were detected by enzyme-linked immunosorbent assay kit;the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated-PI3K(p-PI3 K),protein kinase B(AKT),p-AKT,nuclear factor(NF)-κB p65,p-NF-κB p65 were detected by Western blotting.Results The TT of sham operation group,model group,experimental-L,-H groups and experimental-H+agonist group were(14.88±1.32),(10.02±0.95),(12.65±1.22),(14.70±1.36)and(10.64±1.21)s;IL-1β were(154.23±13.45),(356.69±31.17),(268.62±23.58),(199.64±20.87)and(337.48±31.46)pg·mL-1;ET-1 were(6.78±0.68),(14.43±1.14),(11.23±1.07),(8.20±0.81)and(13.33±1.27)pg·mL-1;p-PI3K/PI3K were 0.36±0.04,0.76±0.07,0.59±0.05,0.44±0.04 and 0.69±0.07;p-AKT/AKT were 0.52±0.05,0.90±0.09,0.74±0.08,0.61±0.06 and 0.86±0.08;p-NF-κB p65/NF-κB p65 were 0.28±0.03,0.95±0.04,0.69±0.07,0.35±0.05 and 0.87±0.08,respectively.There were statistically significant differences between model group and sham operation group(all P＜0.05);the above indexes in experimental-L group and experimental-H group were significantly different from those in medel group(all P＜0.05);the above indexes in experimental-H+agonist group were significantly different from those in experimental-H group(all P＜0.05).Conclusion PAE may improve disease progression in TAO rats by inhibiting the PI3K/AKT/NF-κB signaling pathway.