BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.

Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

ObjectiveTo investigate the expression level of lysophosphatidyllecithin acyltransferase 4 （LPCAT4） in pancreatic cancer and its effect on the proliferation of pancreatic cancer cells. MethodsIn this study， the differentially expressed genes of patients with KRAS mutant and wild-type pancreatic cancer were analyzed by online database LinkedOmics. The LPCAT4 expression in pancreatic cancer tissues was analyzed online by the University of Alabama at Birmingham Cancer Data Analysis （UALCAN）， Sangerbox and gene expression profile interaction analysis 2 （GEPIA2）. Kaplan-Meier Plotter database was used to explore the correlation between LPCAT4 and the prognosis of patients with pancreatic cancer. The expression of LPCAT4 in human pancreatic cancer cells were detected by quantitative real-time PCR and Western blot analysis. LPCAT4 was knocked down in the high-expressing SW1990 cell line and overexpressed in the low-expressing MIA PaCa-2 cell line. The effects of LPCAT4 expression on cell proliferation were assessed using CCK-8 and EdU assays. STRING and GEPIA2 databases were used to obtain LPCAT4 binding and coexpressed genes in tumors， which were then analyzed by GO and KEGG. ResultsAnalysis of the LinkedOmics online database revealed a significant upregulation of LPCAT4 in patients with KRAS mutant pancreatic cancer compared to patients with KRAS wild-type pancreatic cancer. The online analysis of GEPIA2， UALCAN and Sangerbox 3.0 showed that the expression of LPCAT4 was higher in pancreatic cancer than in normal tissues. Analysis of the Kaplan-Meier Plotter database revealed that high LPCAT4 expression was associated with poorer prognosis in pancreatic cancer patients.Western blot and qPCR results showed that expression of LPCAT4 in pancreatic cancer cell lines was significantly higher than in normal pancreatic ductal epithelial cells. Knockdown of LPCAT4 in SW1990 cells inhibited proliferation， while overexpression in MIA PaCa-2 cells promoted proliferation. Enrichment analysis indicated that LPCAT4 was closely related to sulfur metabolism. ConclusionsLPCAT4 is highly expressed in pancreatic cancer and is associated with poor prognosis of patients. It plays a significant regulatory role in the proliferation of pancreatic cancer cells， with its expression level closely correlated with cell proliferation capacity. These findings reveal the critical role of LPCAT4 in the malignant progression of pancreatic cancer and provide important evidence for its potential as a therapeutic target.

Objective To mine the adverse drug events(ADE)signal of avatrombopag,an effective drug for thrombocytopenia treatment,based on real world data in order to provide reference for its clinical safety application.Methods The OpenVigil2.1 pharmacovigilance platform was used to obtain the ADE report data of avatrombopag from May 2018 to March 2023 in the database of FDA adverse event reporting system(FAERS).The ADE signals were classified and described by the system organ class(SOC)and preferred term(PT)of the ADE terminology set in the Medical Dictionary for Regulatory Activities(MedDRA),and reporting odds ratio(ROR)and UK Medicines and Healthcare Products Regulatory Agency(MHRA)comprehensive standard were used to detect the positive ADE signals.Results A total of 1 879 ADE reports related to avatrombopag were obtained,24 SOCs were involved,and 28 positive ADE signals were detected at PT level.Among these signals,the strongest ones were renal vein thrombosis,portal vein thrombosis and graft versus host disease,while the reports accounting for the largest numbers were headache,fatigue and asthenia.There were 8 ADE signals discovered newly,that is,seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea.Conclusion For clinical use of avatrombopag,clinicians should not only concern the risk of thrombosis,but also pay close attention to ADE signals such as seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea that are not documented in the instructions.

Objective To observe the clinical efficacy of acupuncture on ghost points combined with Longdan Xiegan Decoction in the treatment of post-stroke insomnia of liver-fire disturbing the heart type.Methods Sixty patients with liver-fire disturbing the heart type of post-stroke insomnia were randomly divided into observation group and control group,with 30 patients in each group.The control group was given oral use of modified Longdan Xiegan Decoction,and the observation group was given acupuncture at the ghost points on the basis of the treatment of the control group.Both groups were treated for 4 weeks.After 1 month of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Pittsburgh Sleep Quality Index(PSQI)score and the Athens Insomnia Scale(AIS)score were observed before and after treatment in the two groups.The changes of Self-Rating Depression Scale(SDS)scores were compared before and after treatment in the two groups of patients.Results(1)After treatment,the PSQI scores of the two groups of patients were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the PSQI scores,with a statistically significant difference(P＜0.05).(2)After treatment,the AIS scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the AIS scores,and the difference was statistically significant(P＜0.05).(3)After treatment,the SDS scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving SDS scores,and the difference was statistically significant(P＜0.05).(4)The total effective rate of the observation group was 86.66%(26/30),while that of the control group was 76.66%(23/30).The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion Acupuncture at the ghost points combined with Longdan Xiegan Decoction for the treatment of liver-fire disturbing the heart type of post-stroke insomnia can significantly improve the clinical symptoms of the patients,and the therapeutic effect is remarkable.

Objective Data mining technology was used to mine the medication rules of the prescriptions used in the treatment of pediatric atopic dermatitis by Chinese medical master XUAN Guo-Wei.Methods The medical records of effective cases of pediatric atopic dermatitis treated by Professor XUAN Guo-Wei at outpatient clinic were collected,and then the medical data were statistically analyzed using frequency statistics,association rule analysis and cluster analysis.Results A total of 242 prescriptions were included,involving 101 Chinese medicinals.There were 23 commonly-used herbs,and the 16 high-frequency herbs(frequency＞100 times)were Glycyrrhizae Radix et Rhizoma,Saposhnikoviae Radix,Glehniae Radix,Perillae Folium,Ophiopogonis Radix,Cynanchi Paniculati Radix et Rhizoma,Microctis Folium,Dictamni Cortex,Scrophulariae Radix,Coicis Semen,Cicadae Periostracum,Lilii Bulbus,Rehmanniae Radix,Kochiae Fructus,Sclerotium Poriae Pararadicis,and Euryales Semen.The analysis of the medicinal properties showed that most of the herbs were sweet and cold,and mainly had the meridian tropism of the spleen,stomach and liver meridians.The association rule analysis yielded 24 commonly-used drug combinations and 20 association rules.Cluster analysis yielded 2 core drug combinations.Conclusion For the treatment of pediatric atopic dermatitis,Professor XUAN Guo-Wei focuses on the clearing,supplementing and harmonizing therapies,and the medication principle of"supporting the healthy-qi to eliminate the pathogen,and balancing the yin and yang"is applied throughout the treatment.

Objective To analyze the treatment strategy of the atrial septal defect in the surgical treatment of Ebstein's anomaly combined with the atrial septal defect and the short-term follow-up results of the treatment of Ebstein's anomaly.Methods A retrospective analysis of the clinical data and follow-up results of 20 patients with Ebstein's anomaly and atrial septal defect was conducted from September 2017 to February 2021.And the statistical analysis on the preoperative and postoperative echocardiography results of this group of patients was performed.Results Sixteen patients underwent the biventricular correction surgery,among whom two cases underwent the horizontal atrial tricuspid valvuloplasty(Danielsons procedure),four cases underwent the vertical atrial tricuspid valvuloplasty(Carpentier procedure),and ten cases underwent the conical reconstruction.Two patients were given a half ventricular correction surgery(tricuspid valve reconstruction combined with bidirectional Glenn surgery)and two patients underwent the bidirectional Glenn surgery.The combined atrial septal defects were closed in one stage during extracorporeal circulation for correction of deformitie in 20 patients.At 1,3,6,and 12 months after the surgery,the patient's right ventricular size significantly decreased compared to preoperative(P<0.05),and cardiac function(left ventricular ejection fraction)significantly improved(P<0.05).Conclusion The surgical treatment of Ebstein's anomaly combined with the atrial septal defect should follow the principle of individualized treatment.Biventricular correction is still the first choice for the treatment of Ebstein's anomaly,and the atrial septal defect should be closed at one stage,so as to obtain a good therapeutic effect.

Objective To construct reference ranges of cardiac size and morphologic parameters in low-risk fetuses at 28-39 gestational weeks using two-dimensional speckle tracking technique.Methods A prospective collection of 453 low-risk singleton pregnancies with echocardiography at Obstetrics and Gynecology Hospital,Fudan University was used to assess the size(length,width,and area)and morphology(sphericity index,i.e.,the ratio of length to width)of the fetal four-chamber view and two ventricles using two-dimensional speckle tracking technique.Repeated inter-and intra-observer agreement of measurements was assessed using the intraclass correlation coefficients(ICCs).Statistical analysis of cardiac measurement parameters was performed to establish reference ranges of values for cardiac size and morphology in low-risk fetuses.Results The inter-and intra-group ICCs for reproducibility tests of fetal cardiac parameters measurements were 0.691 to 0.980.Fetal four-chamber view and ventricular size increased with gestational week(all P<0.001),the end-diastolic length of the left ventricle was larger than that of the right ventricle,and the end-diastolic diameter was smaller than that of the right ventricle(both P<0.001),while there was no significant difference in the end-diastolic area of the two ventricles(P= 0.050).The spherical index of four-chamber view did not correlate with gestational week(P=0.811).The sphericity index of the basal and intermediate segments of the left ventricle was greater than that of the right ventricle,and the sphericity index of the apical segment was less than that of the right ventricle,the differences were statistically significant(all P<0.01).Conclusion The two-dimensional speckle tracking technique for measuring fetal cardiac parameters has good reproducibility.The reference ranges for cardiac size and morphology in low-risk fetuses developed in this study will be useful for prenatal evaluation of cardiac remodeling.

Objective To explore the risk factors of frozen shoulder,and to provide the basis for the prevention of frozen shoulder.Methods A total of 114 patients with frozen shoulder who were hospitalized in the First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to August 2022 were included in case group,and 114 physical examination patients with no history of frozen shoulder were included in control group.The clinical data of two groups were collected and the risk factors of frozen shoulder were analyzed by multivariate Logistic regression.Results There were statistically significant differences in cervical radiculopathy,type 2 diabetes mellitus,hepatitis,chronic non-atrophic gastritis,lumbar disc herniation,osteoporosis and thyroid sarcoidosis between two groups(P<0.05).Multivariate Logistic analysis showed that cervical radiculopathy(OR=6.114,95%CI:1.458-25.642)and type 2 diabetes mellitus(OR=24.069,95%CI:4.023-144.007)were independent risk factors for the onset of frozen shoulder.Conclusion Patients with type 2 diabetes mellitus and cervical radiculopathy have a higher risk of frozen shoulder,and should pay attention to early prevention.

Objective To investigate the influencing factors of vancomycin in the area under curve for 24 h(AUC0-24h)in patients after orthopedic surgery,and to predictive and analyze a good pharmacokinetic model for AUC0-24h Methods Patients who underwent orthopedic surgery and used vancomycin in The Sixth Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2022 were included,and the basic information,the medication,the blood and biochemical indexes of the patients were collected to analyze the factors affecting postoperative vancomycin AUC0-24h in orthopedic surgery.The AUC0-24h was calculated using the first-level pharmacokinetic formula,the JavaPK? for Desktop(JPKD)and the vancomycin daily dose elimination rate formula.Results 91 patients were finally included,and the cystatin C(OR=189.168,P=0.005)and the single dose(OR=19.160,P＜0.001)were independent protective factors for vancomycin AUC0 24 h in postoperative orthopedic patients,and the retinol binding protein was an independent risk factor for vancomycin AUC0-24h(OR=0.910,P＜0.05).By predicting and analyzing the model of vancomycin AUC0 24h in postoperative orthopedic patients,the absolute percentage error of both JPKD software and vancomycin daily dose elimination rate formula were lower than 30％.The intraclass correlation efficient between the AUC0 24h of the JPKD software and vancomycin daily dose elimination rate formula,and the AUC0 24h of the first-level pharmacokinetic formula were 0.781 and 0.524,respectively.Conclusion Cystatin C is an important factor influencing vancomycin AUC0-24h in postoperative orthopedic patients,and JPKD software is more suitable for predicting vancomycin AUC0-24h after orthopedic surgery than the vancomycin daily dose elimination rate formula method.