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 effectiveness of using 3 hollow compression screws combined with 1 screw off-axis fixation under the guidance of three-dimensional (3D) printed guide plate with mortise-tenon joint structure (mortise-tenon joint plate) for the treatment of Pauwels type Ⅲ femoral neck fractures. METHODS: A clinical data of 78 patients with Pauwels type Ⅲ femoral neck fractures, who were admitted between August 2022 and August 2023 and met the selection criteria, was retrospectively analyzed. The operations were assisted with mortise-tenon joint plates in 26 cases (mortise-tenon joint plate group) and traditional guide plates in 28 cases (traditional plate group), and without guide plates in 24 cases (control group). There was no significant difference in the baseline data of gender, age, body mass index, cause of injury, and fracture side between groups ( P>0.05). The operation time, intraoperative blood loss, frequency of intraoperative fluoroscopy, incision length, incidence of postoperative deep vein thrombosis of lower extremity, pain visual analogue scale (VAS) score at 1 week after operation, and Harris score of hip joint at 3 months after operation were recorded and compared. X-ray re-examination was taken to check the quality of fracture reduction, fracture healing, and the shortening length of the femoral neck at 3 months after operation, and the incidences of internal fixation failure and osteonecrosis of the femoral head during operation. RESULTS: Compared with the control group, the operation time, intraoperative blood loss, and frequency of intraoperative fluoroscopy reduced in the two plate groups, and the quality of fracture reduction was better, but the incision was longer, and the differences were significant ( P<0.05). The operation time and intraoperative blood loss were significantly higher in the traditional plate group than in the mortise-tenon joint plate group ( P<0.05), the incision was significantly longer ( P<0.05); and the difference in fracture reduction quality and the frequency of intraoperative fluoroscopy was not significant between two plate groups ( P>0.05). There was 1 case of deep vein thrombosis of lower extremity in the traditional plate group and 1 case in the control group, while there was no thrombosis in the mortise-tenon joint plate group. There was no significant difference in the incidence between groups ( P>0.05). All patients were followed up 12-15 months (mean, 13 months). There was no significant difference in VAS score at 1 week and Harris score at 3 months between groups ( P>0.05). Compared with the control group, the fracture healing time and the length of femoral neck shortening at 3 months after operation were significantly shorter in the two plate groups ( P<0.05). There was no significant difference between the two plate groups ( P>0.05). There was no significant difference in the incidences of non-union fractures, osteonecrosis of the femoral head, or internal fixation failure between groups ( P>0.05). CONCLUSION For Pauwels type Ⅲ femoral neck fractures, the use of 3D printed guide plate assisted reduction and fixation can shorten the fracture healing time, reduce the incidence of postoperative complications, and be more conducive to the early functional exercise of the affected limb. Compared with the traditional guide plate, the mortise-tenon joint plate can reduce the intraoperative bleeding and shorten the operation time.
Humans ; Femoral Neck Fractures/diagnostic imaging* ; Bone Plates ; Fracture Fixation, Internal/instrumentation* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Bone Screws ; Adult ; Aged ; Treatment Outcome ; Printing, Three-Dimensional ; Operative Time

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.

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 Based on the three tools of the AGREE Next Steps Consortium(AGREE Ⅱ),China Clinical Guidelines Evaluation System(AGREE-China)and Scientificity Transparency Applicability Rankings(STAR),the methodological quality of Chinese medicine clinical treatment guidelines for coronary heart disease published by domestic institutions was systematically evaluated.Methods Computer system retrieval of China National Knowledge Infrastructure(CNKI),WanFang Data,Chinese Science and Technology Journal Database(VIP),China Biology Medicine(CBM)and Yimai Tong,and collect clinical practice guidelines of traditional Chinese medicine for coronary heart disease issued by domestic institutions(including expert consensus).The search period was from the establishment of the database to December 31,2023.Results A total of 21 guidelines were included.AGREE Ⅱ recommended 13 for grade A and 8 for grade B.The approval-China review strongly recommends 12,weakly recommends 8,and does not recommend 1.The highest STAR rating is a 4.0 star recommendation and the lowest is a 1.5 star recommendation.Conclusions There are a large number of TCM diagnosis and treatment guidelines and expert consensus on coronary heart disease in China,but the quality is uneven.It is suggested that the future guideline formulation should pay attention to the evidence-based principle,promote the standardization and standardization of the guideline formulation,and improve the scientific and applicability of the guideline.

Objective Based on the three tools of the AGREE Next Steps Consortium(AGREE Ⅱ),China Clinical Guidelines Evaluation System(AGREE-China)and Scientificity Transparency Applicability Rankings(STAR),the methodological quality of Chinese medicine clinical treatment guidelines for coronary heart disease published by domestic institutions was systematically evaluated.Methods Computer system retrieval of China National Knowledge Infrastructure(CNKI),WanFang Data,Chinese Science and Technology Journal Database(VIP),China Biology Medicine(CBM)and Yimai Tong,and collect clinical practice guidelines of traditional Chinese medicine for coronary heart disease issued by domestic institutions(including expert consensus).The search period was from the establishment of the database to December 31,2023.Results A total of 21 guidelines were included.AGREE Ⅱ recommended 13 for grade A and 8 for grade B.The approval-China review strongly recommends 12,weakly recommends 8,and does not recommend 1.The highest STAR rating is a 4.0 star recommendation and the lowest is a 1.5 star recommendation.Conclusions There are a large number of TCM diagnosis and treatment guidelines and expert consensus on coronary heart disease in China,but the quality is uneven.It is suggested that the future guideline formulation should pay attention to the evidence-based principle,promote the standardization and standardization of the guideline formulation,and improve the scientific and applicability of the guideline.

Objective:To explore the clinical features, treatment, prognosis and genetic mutation in neonatal congenital hyperinsulinemia(CHI).Methods:Neonates with CHI admitted to the neonatal intensive care unit of Hebei Provincial Children′s Hospital from February 2017 to August 2020 were selected, and their clinical characteristics, diagnosis and treatment, prognosis and genetic mutation were retrospectively analyzed.Results:A total of seven neonates were enrolled.The average gestational age was(38.1±1.5)weeks with two cases gestational age<37 weeks.The mean birth weight was(3 608±906)g with three cases birth weight>4 000 g. The common clinical manifestations included lethargy, poor feeding, cyanosis, seizures, and tremble.Non-specific manifestations were observed in two premature infants, whose blood glucose were found very low during the routine monitoring at 1 hour and 3 hours after birth respectively.Among the seven cases, six cases needed high glucose infusion rate(GIR)[>10 mg/(kg·min)] to maintain the serum glucose at the normal level from the beginning.Only one case needed lower GIR[3-5 mg/(kg·min)] on admission while gradually increased to 8 mg/(kg·min) maximumly during hospitalization.All seven neonates were treated with diazoxide orally, and two cases(2/7) were effective, including one case who discontinued the drug at six months after birth with normal blood glucose level.The remaining five neonates(5/7) were diazoxide resistant due to mutations in the ABCC8 gene encoding the K ATP+ -channel of the pancreatic beta cell and then treated with octreotide.Two cases(2/5) of them were effective to octreotide and the other three cases(3/5) were both diazoxide and octreotide resistant.One case died after withdrawal from the treatment and the other one lost follow-up.The other five cases were followed up until now.Normal neurological development were found in three cases.Two cases were found with epilepsy and moderate developmental delay in language and social competence ability during the follow up.Mutations in ABCC8 were the most common in seven cases, of which six cases were heterozygous mutation of ABCC8 and one case was heterozygous mutation of GLUDI. Conclusion:The clinical manifestations of CHI are non-specific.The blood glucose level of the high-risk neonates should be timely monitored.Neonates who needs lower GIR[<8 mg/(kg·min)] at the early stage can not be completely excluded CHI.Some CHI cases may self-resolved after several months.Molecular diagnosis can identify the pathogenic genes, which is important to achieve accurate diagnosis and treatment, and thus improve the prognosis of patients with CHI.

Objective:To investigate the icariin on cognitive function and astrocytic pyroptosis in hemorrhagic shock resuscitation model mice.Methods:Forty-eight SPF grade C57BL/6 mice (male) were randomly divided into four groups ( n=12 in each group): Sham operation control group (Group C), hemorrhagic shock and resuscitation group (Group H), hemorrhagic shock and resuscitation plus icariin group (Group HI) and hemorrhagic shock resuscitation plus icariin and SSK1 group (Group HIS, SSK1 was a phosphorylation agonist of mitogen-activated protein kinase p38(p38MAPK). The mice in Group H, HI and HIS were subjected to hemorrhagic shock and resuscitation model by bleeding and retransfusion via left femoral vein; the mice in Group HI and HIS were administered with icariin (10 mg/kg) intragastrically for 7 days; the mice in Group C and H were administered with the same amount of normal saline containing dimethyl sulfoxide(DMSO). The mice in Group HIS were administered with SSK1 (0.5 mg/kg) intraperitoneally, but the mice in Group C, H and HI were only administered with the same amount of normal saline containing DMSO.At 15 days after resuscitation, novel objective recognition test and fear conditioning test were used to assess cognitive dysfunction of mice.Microtubule-associated protein 2(MAP2), a specific marker protein of neurons reflecting astrocytic pyroptosis in the hippocampus of mice, were detected by immunofluorescence assay so as to assess neuronal injury and astrocytic pyroptosis.The levels of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the hippocampus were evaluated by Western blot.SPSS 21.0 software was used for data analysis, multiple samples among groups were compared by one-way ANOVA, and SNK- q test was used for further pairwise comparison. Results:The results of new object recognition test showed that the difference of new object recognition index among the four groups was statistically significant ( F=50.75, P<0.05). The new object recognition indexes in H group(22.7±6.9), HI group(40.1±7.0) and HIS group (22.5±7.5) were significantly lower than that in C group (58.5±11.2). The index in HI group was higher than that in H group, while the index in HIS group was lower than that in HI group (all P<0.05). The results of the fear conditioning test showed that there was a statistically significant difference in the percentage of freezing time among the four groups of mice ( F=60.54, P<0.05). And the percentage of freezing time in H group((21.8±5.0)%), HI group ((38.4±7.4) %)and HIS group((21.3±4.2)%)were lower than that in C group((49.1±7.0)%), which in HI group was higher than that in H group ( P<0.05)and which in HIS group was lower than that in HI group(all P<0.05). The results of immunofluorescence showed that there were significant decreases of MAP2 intensity ((35.3±9.3)%, (63.3±6.1)%, (28.7±10.3)%) but increases of pyroptotic astrocytes ((24.5±4.2)%, (9.3±1.5)%, (22.1±3.3)%) in the H, HI and HIS groups compared with those of C group ((106.7±19.7) %, (3.4±2.0)%). There was an increase of MAP2 intensity but a decrease of pyroptotic astrocytes in the HI group compared with those in H group, and there was a decrease of MAP2 intensity but an increase of pyroptotic astrocytes in the HIS group compared with those of HI group (all P<0.05). The Western blot results showed that there were significant increases of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the H, HI and HIS groups compared with C group, there were decreases of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the HI group compared with H group, and there were increases of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the HIS group compared with those in HI group (all P<0.05). Conclusion:Icariin alleviates hemorrhage shock and resuscitation-induced cognitive dysfunction and astrocytic pyroptosis in mice, and the mechanism may be associated with inhibition of phosphorylated p38MAPK.

Objective:To identify the risk factors for failure in closed reduction of flexed supracondylar humerus fractures of Wilkins type Ⅲ in children.Methods:The data of 171 children were retrospectively analyzed who had been treated for flexed supracondylar humerus fractures of Wilkins type Ⅲ from January 2013 to December 2021 at Department of Orthopaedics, Children's Hospital of Jiangxi Province and Children's Hospital of Fudan University Anhui Hospital. They were divided into a reduction failure group (35 cases) and a reduction success group (136 cases). Factors such as fracture height, age, body mass index, ulnar-radial offset direction, obvious axial rotation of the distal fracture fragment, combined ulnar nerve injury, and time from injury to operation were listed as risk factors. The independent risk factors for failure in closed reduction of flexed supracondylar humerus fractures were identified by univariate analysis of variance and multi-variate logistic regression analysis.Results:The average age of 171 children was (7.8±2.6) years. There were 151 cases of radial deviation and 20 cases of ulnar deviation, 120 high type fractures and 51 low type fractures, and 20 cases of combined ulnar nerve injury and 115 cases of obvious rotation of the distal fracture fragment. The one-way ANOVA showed statistically significant differences between the reduction failure group and the reduction success group in terms of age, obvious rotation of the distal fracture fragment, and ulnar nerve injury ( P<0.05), but no significant differences in fracture height, body mass index, ulnar-radial offset direction, or time from injury to operation ( P>0.05). Multivariate logistic regression analysis showed that obvious rotation of the distal fracture fragment ( OR=3.287, 95% CI: 1.136 to 9.513, P=0.028) and combined ulnar nerve injury ( OR=6.439, 95% CI: 2.262 to 18.327, P=0.001) were risk factors for failure in closed reduction. Conclusion:As obvious rotation of the distal fracture fragment and combined ulnar nerve injury may be independent risk factors for failure in closed reduction of flexed supracondylar humerus fractures of Wilkins type Ⅲ in children, they should arouse more attention in the treatment of such fractures.

Objective:To explore the safety and efficacy of laparoscopic microwave ablation combined with partial nephrectomy in the treatment of cystic renal masses.Methods:The 19 patients with cystic renal masses undergoing laparoscopic microwave ablation combined with partial nephrectomy from November 2017 to December 2019 were retrospectively analyzed. There were 13 males and 6 females. The average age was 46.2 years. The mean body mass index was (25.8±3.1) kg/m 2. The masses located in the left kidney in 7 cases and the right kidney in 12 cases. The ECOG scores were 0. The mean maximum diameter of the tumors was (2.8±1.3) cm. Five cases were diagnosed with Bosniak Ⅲ and 14 cases with Bosniak Ⅳ. According to R. E.N.A.L. scoring, 11 cases were of low difficulty (4-6 points), 7 cases of medium difficulty (7-9 points) and 1 case of high difficulty (10-12 points). The cystic renal masses were ablated by laparoscopic microwave ablation, then followed by partial nephrectomy. Postoperative complications were observed and the prognosis was assessed by CT or MRI. Results:The mean duration of operation was (84.0±20.8) min. The median intraoperative blood loss was 20 (10-50) ml. The median duration of postoperative hospitalization was 3 (2-6) d, and no complications such as bleeding, infection, gross hematuria or urine leakage were observed. According to the malignant degree of cystic renal masses, the patients were divided into low-risk group and high-risk group. The patients with benign cystic kidney tumors or with low biological malignancy were considered as the low-risk group, while the patients with high malignant pathology were considered as the high-risk group. In the low-risk group, there were 4 patients, including 1 patient with papillary adenoma, 1 patient with renal angiomyolipoma, 1 patient with low-grade malignant potential multilocular cystic renal tumor, and 1 patient with renal chromophobe carcinoma (stage T 1a). In the high-risk group, there were 15 cases, including 14 cases of clear cell renal cell carcinoma (AJCC pathological stage: T 1a stage 11 cases, T 1b stage 3 cases; WHO/ISUP classification: 7 cases in grade 1, 6 cases in grade 2, and 1 case in grade 3); 1 case of Type 2 papillary renal cell carcinoma (stage T 1b, grade 2). The median follow-up was 20 months (12-37 months). Both groups survived, and no signs of tumor recurrence, implantation or metastasis were found in chest and abdomen imaging. Blood tests were performed regularly, and no significant abnormalities occurred. Conclusions:The safety and efficacy of laparoscopic microwave ablation combined with partial nephrectomy for the treatment of cystic renal masses is satisfactory, and postoperative pathology is clear, providing a potential option for cystic renal masses treatment.