OBJECTIVE To investigate the effects of osthole(OST)on skin wound healing and angiogenesis in rats by regulating the sonic hedgehog(SHH)signaling pathway.METHODS Full-layer skin defect wound model rats were established and then randomly separated into Model group,OST low-dose,medium-dose and high-dose groups(OST-L group,OST-M group,OST-H group,20,30,40 mg/kg OST),high-dose OST+SHH inhibitor cyclopamide group(OST-H+cyclopamide group,40 mg/kg OST+10 mg/kg cyclopamide),with 12 rats in each group.Another 12 rats were selected as the control group.The wound healing of rats on 1,7 and 14 days of administration was observed,and the wound healing rate of rats in each group was measured.The pathological changes and collagen deposition in rat wound tissue were observed;the levels of angiopoietin-1(Ang-1)and basic fibroblast growth factor(bFGF)in wound tissue of rats were detected;the relative expressions of vascular endothelial growth factor A(VEGFA)and vascular endothelial growth factor receptor-2(VEGFR-2)mRNA were also detected in wound tissue of rats;the protein expressions of VEGFA,VEGFR-2,SHH and glioma-associated oncogene homolog-1(GLI1)were determined in wound tissue of rats.RESULTS Compared with Model group,the healing rate of skin wound,relative expression of collagen protein,the levels of Ang-1 and bFGF,the mRNA and protein expressions of VEGFA and VEGFR-2,and the protein expressions of SHH and GLI1 were all significantly increased in OST-M and OST-H groups(P＜0.05).The wound tissue underwent significant re-epithelialization,with reduced inflammatory cell infiltration and granulation tissue edema,and an increase in the number of new blood vessels.SHH inhibitor cycloparamide weakened the promoting effects of OST on skin wound healing and angiogenesis in rats.CONCLUSIONS OST may promote skin wound healing and angiogenesis in rats by activating the SHH signaling pathway.

Intracranial germ cell tumors (iGCT) is a common cause of delayed puberty (DP).　A retrospective analysis was conducted on the clinical data of two patients with DP caused by iGCT. The disease characteristics of the two patients included DP, primary amenorrhea, growth retardation, short stature, subclinical hypothyroidism, etc. They were diagnosed as DP through imaging and related biochemical tests, and some sex hormone drugs were given on the basis of active treatment of the primary disease. Two patients had varying degrees of development in height, weight and secondary sexual characteristics, and further treatment condition is being tracking by us. Early identification and appropriate clinical intervention are of great significance to the reproductive endocrine function, bone health and long-term health such as terminal height of DP patients.

Intracranial germ cell tumors (iGCT) is a common cause of delayed puberty (DP).　A retrospective analysis was conducted on the clinical data of two patients with DP caused by iGCT. The disease characteristics of the two patients included DP, primary amenorrhea, growth retardation, short stature, subclinical hypothyroidism, etc. They were diagnosed as DP through imaging and related biochemical tests, and some sex hormone drugs were given on the basis of active treatment of the primary disease. Two patients had varying degrees of development in height, weight and secondary sexual characteristics, and further treatment condition is being tracking by us. Early identification and appropriate clinical intervention are of great significance to the reproductive endocrine function, bone health and long-term health such as terminal height of DP patients.

The prevalence of osteoporosis， osteoarthritis， gouty arthritis， rheumatoid arthritis， and intervertebral disc degeneration is increasing year by year with the growing number of elderly people， and the common clinical manifestations of these diseases include severe pain in different areas， which seriously affects the daily life of the patients. Therefore， how to relieve the pain and reduce the prevalence of bone and joint diseases and improve the quality of life of the patients is a hot spot in the medical field. Studies have confirmed that NOD-like receptor family， pyrin domain-containing protein 3 （NLRP3） inflammasomes， as pattern recognition receptors， are involved in the inflammation， chondrocyte proliferation， osteoblast and osteoclast differentiation， intervertebral disc cell inflammation and scorching， extracellular matrix degradation and apoptosis， mitochondrial dysfunction， endoplasmic reticulum stress， and reactive oxygen species damage， demonstrating close link with the development of bone and joint diseases. Chinese medicine has a long history and demonstrates remarkable therapeutic effects in the treatment of bone and joint diseases. It can mitigate the pathological changes of bone and joint diseases by inhibiting NLRP3 inflammasomes to alleviate the pain， playing a role in preventing and treating these diseases. Therefore， this paper briefly describes the relationship between NLRP3 inflammasomes and the development of bone and joint diseases by reviewing the latest research progress at home and abroad. We summarize the latest studies about the active components， extracts， and compound prescriptions of Chinese medicines in the treatment of bone and joint diseases via regulating NLRP3 inflammasomes. This review is expected to offer new insights into the in-depth research on the pathogenesis and drug treatment of bone and joint diseases and provide a basis for the clinical application of Chinese medicine in the prevention and treatment of such diseases.

Objective To compare the effects of different statistical protocols on the results of external quality assessment(EQA)of se-men,and select appropriate statistical protocols for the promotion of EQA of semen.Methods Taking sperm concentration as an ex-ample,the semen EQA data of 20 laboratories in Hunan Province in 2022 were selected,and the advantages and disadvantages of the traditional statistical scheme(TSS),robust statistical scheme(RSS)and traditional statistical scheme after eliminating the"outliers"(TSEOS)combined with robust statistical technology were analyzed and compared.Results The"outliers"could not be excluded from the sperm concentration data of the four groups in the TSS,which led to the difference between TSS and RSS or TSEOS.The num-ber of qualified laboratories for TSS and RSS were 19 vs 16,19 vs 16,19 vs 19,and 19 vs 19,respectively.Conclusion The results of RSS are similar to those of TSEOS.Compared with TSS,RSS do not need to remove outlier data steps,and are more suitable for se-men EQA data analysis with small data volume.

Objective:To explore the risk factors of thyroid nodules in diabetic patients and its correlation with Traditional Chinese Medicine (TCM) constitution.Methods:A Total of 213 cases of diabetic patients in Guang’anmen Hospital and Tangshan Hospital from January 2019 to August 2020 were choosen to do the questionnaire, with containly symptom and constitution. The patients were divided into diabetes with thyroid nodules group and diabetes without thyroid nodules group according to whether thyroid nodules were combined. We compared the clinical data characteristics of 2 groups, and used multi-factor logistic regression model to analyze the risk factors of diabetic patients with thyroid nodules and their correlation with TCM constitutions. Results:Diabetes patients aged from 50-80 years old [ OR=2.949, 95% CI (1.266-6.714)], females [ OR=3.736, 95% CI (1.823-1.541)], diabetes duration≥15 years [ OR=1.558, 95% CI (1.623-1.585)], elevated HbA1c [ OR=5.862, 95% CI (1.418-23.629)], elevated VLDL [ OR=2.851, 95% CI (1.597-6.824)], frequent insomnia [ OR=1.970, 95% CI (1.315-3.395)], Qi stagnation [ OR=4.357, 95% CI (2.634-8.377)], blood stasis [ OR=4.420, 95% CI (1.874-15.258)] are more likely to suffer from thyroid nodules ( P<0.05). Conclusion:Diabetic patients aged from 50-80 years old, females, diabetes duration≥15 years, elevated HbA1c, family history of thyroid nodules, frequent insomnia, and mood swings are more likely to develop thyroid nodules; qi stagnation and blood stasis are dangerous constitutions for diabetic patients with thyroid nodules.

Objective:To explore the effects of platelet parameters, coagulation indexes, platelet and lymphocyte ratio (PLR) values, neutrophil and lymphocyte ratio (NLR) values on coagulation disorders and perinatal outcomes in pregnant women with intrahepatic cholestasis of pregnancy (ICP).Methods:A retrospective analysis of prothrombin time (PT) and activated partial thromboplastin time (activated partial) of 106 ICP patients (ICP group) and 138 normal pregnant women (control group) delivered from Gansu Provincial People's Hospital from January 2017 to December 2018 was performed. Activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer (D-D), platelet count, mean platelet volume (MPV), platelet distribution red blood cell distribution width (RDW), number of white blood cell (WBC), PLR, NLR, and postpartum hemorrhage and perinatal outcomes were compared between the two groups. Further based on whether serum bile acid (TBA) was ≥40 μmol/L, the patients in ICP group were divided into mild ICP subgroup and severe ICP subgroup, and the changes in the difference indicators were analyzed between the two subgroups.Results:Compared with control group, MPV ( t=4.929, P<0.001), FIB ( t=3.509, P<0.001), D-D ( t=7.834, P<0.001) and NLR ( t=4.098, P<0.001) were significantly increased in ICP group ( P<0.05). Platelet count ( t=4.367, P<0.001) and PLR ( t=2.448, P=0.015) were significantly decreased in ICP pregnant women. The incidence of postpartum hemorrhage ( t=10.003, P<0.001), fetal distress (χ 2=17.194, P<0.001), preterm birth rate (χ 2=13.938, P<0.001) and transfer into neonatal intensive care unit (NICU)(χ 2=29.736, P<0.001) in ICP group was higher than that in control group. Apgar score ( t=3.234, P=0.001) and neonatal birth weight ( t=6.509, P<0.001) in ICP group were lower than those in control group. Further analysis of ICP components for severe ICP and mild ICP revealed significant differences in MPV ( t=2.376, P=0.019), FIB ( t=2.174, P=0.032), D-D ( t=3.074, P=0.003), WBC ( t=2.021, P=0.046), neutrophil count ( t=2.131, P=0.035), NLR ( t=2.864, P=0.005), etc. Postpartum hemorrhage ( t=3.257, P=0.002), the preterm birth rate (χ 2=4.025, P=0.045), birth weight ( t=3.126, P=0.002), and transfer rate to the NICU (χ 2=5.518, P=0.019) were also significantly different between the two groups. Conclusion:ICP pregnant women have abnormal coagulation and fibrinolysis, which may lead to postpartum hemorrhage. The incidence of poor perinatal outcomes is high, which should be highly valued by the clinic. It is of great significance to evaluate the pregnancy outcome of pregnant women with ICP by analyzing the coagulation function and inflammatory markers of ICP pregnant women.

Objective:To explore the effects of platelet parameters, coagulation indexes, platelet and lymphocyte ratio (PLR) values, neutrophil and lymphocyte ratio (NLR) values on coagulation disorders and perinatal outcomes in pregnant women with intrahepatic cholestasis of pregnancy (ICP).Methods:A retrospective analysis of prothrombin time (PT) and activated partial thromboplastin time (activated partial) of 106 ICP patients (ICP group) and 138 normal pregnant women (control group) delivered from Gansu Provincial People's Hospital from January 2017 to December 2018 was performed. Activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer (D-D), platelet count, mean platelet volume (MPV), platelet distribution red blood cell distribution width (RDW), number of white blood cell (WBC), PLR, NLR, and postpartum hemorrhage and perinatal outcomes were compared between the two groups. Further based on whether serum bile acid (TBA) was ≥40 μmol/L, the patients in ICP group were divided into mild ICP subgroup and severe ICP subgroup, and the changes in the difference indicators were analyzed between the two subgroups.Results:Compared with control group, MPV ( t=4.929, P<0.001), FIB ( t=3.509, P<0.001), D-D ( t=7.834, P<0.001) and NLR ( t=4.098, P<0.001) were significantly increased in ICP group ( P<0.05). Platelet count ( t=4.367, P<0.001) and PLR ( t=2.448, P=0.015) were significantly decreased in ICP pregnant women. The incidence of postpartum hemorrhage ( t=10.003, P<0.001), fetal distress (χ 2=17.194, P<0.001), preterm birth rate (χ 2=13.938, P<0.001) and transfer into neonatal intensive care unit (NICU)(χ 2=29.736, P<0.001) in ICP group was higher than that in control group. Apgar score ( t=3.234, P=0.001) and neonatal birth weight ( t=6.509, P<0.001) in ICP group were lower than those in control group. Further analysis of ICP components for severe ICP and mild ICP revealed significant differences in MPV ( t=2.376, P=0.019), FIB ( t=2.174, P=0.032), D-D ( t=3.074, P=0.003), WBC ( t=2.021, P=0.046), neutrophil count ( t=2.131, P=0.035), NLR ( t=2.864, P=0.005), etc. Postpartum hemorrhage ( t=3.257, P=0.002), the preterm birth rate (χ 2=4.025, P=0.045), birth weight ( t=3.126, P=0.002), and transfer rate to the NICU (χ 2=5.518, P=0.019) were also significantly different between the two groups. Conclusion:ICP pregnant women have abnormal coagulation and fibrinolysis, which may lead to postpartum hemorrhage. The incidence of poor perinatal outcomes is high, which should be highly valued by the clinic. It is of great significance to evaluate the pregnancy outcome of pregnant women with ICP by analyzing the coagulation function and inflammatory markers of ICP pregnant women.

Objective To evaluate 11C-MDA,a cardiac sympathetic nerve presynaptic molecular probe,in acute myocardial ischemia (AMI) and to compare with 13N-Ammonia myocardial perfusion imaging.Methods Twelve Bama miniature pigs were used to establish AMI models.11C-MDA and 13N-Ammonia PET/CT were performed before and after model establishment.The defect fraction,ratio of defect to normal region,defect volume of 11C-MDA and 13N-Ammonia PET/CT were calculated.Paired-t test and twosample t test were used.Results Eight models were established successfully and 4 pigs died.The defect fractions on 11C-MDA and 13N-Ammonia myocardial imaging were significantly different (13.4±3.3 vs 7.4±1.0,18.8±4.4 vs 4.8±1.0,10.5±4.2 vs 4.4±0.9;t values:4.901,8.864,4.030,all P＜0.001) at the first,third and sixth month post-model establishment.The ratios of defect to normal region on 11C-MDA and 13N-Ammonia PET/CT myocardial images were significantly different (0.47±0.14 vs 0.59±0.10,0.43±0.13 vs 0.61±0.09;t values:-2.166,-3.415,both P＜0.05) at the first and third month post-model establishment.The defect volumes on 11C-MDA and 13N-Ammonia PET/CT were significantly different ((4.20±0.34) vs (2.55±0.11) cm3,(10.66±0.71) vs (2.46±0.12) cm3,(5.95±0.50) vs (2.44±0.11) cm3;t values:12.925,32.149,19.440,all P＜0.001) at the first,third and sixth month post-model establishment.Conclusions Myocardial ischemia-reperfusion and cardiac sympathetic restoration might occur at different times.The recovery of myocardial ischemia-reperfusion is earlier than that of the cardiac sympathetic nerve.

Objective To investigate the correlation of single nucleotide polymorphism of rs3731055 and rs2607775 of xeroderma pigmentosum group C (XPC) and smoking with genetic susceptibility to pancreatic cancer.Methods The clinical data of 214 patients with pancreatic cancer who were admitted to the First and Third Affiliated Hospitals of Xinjiang Medical University from January 2009 to June 2011 and 214 healthly individuals were retrospectively analyzed.The samples of venous blood of 214 patients with pancreatic cancer (case group) and 214 healthy individuals (control group) were analyzed by the Multiplex SNaPshot method.The count data were analyzed using the chi-square test.The association between the single nucleotide polymorphism of rs3731055 and rs2607775 with genetic susceptibility to pancreatic cancer was analyzed using the Logistic regression method.Results Four hundred and twenty-three samples of gene were successfully typed,including 210 in the case group and 213 in the control group.The frequency of G allele of XPC rs3731055 was 75.95％ (319/420) in the case group and 77.00％ (328/426) in the control group,with no significant difference between the 2 groups (x2 =0.12,P ＞ 0.05).The frequencies of genotypes GG,GA and AA were 58.57％ (123/210),34.76％ (73/210) and 6.67％ (14/210) in the case group,and 60.09％ (128/213),33.80％ (72/213) and 6.10％ (13/213) in the control group,with no significant difference between the 2 groups (x2=0.12,P ＞ 0.05).The frequency of C allele of XPC rs2607775 was 87.86％ (369/420) in the case group and 93.43％ (398/426) in the control group,with significant difference between the 2 groups (x2=7.75,P ＜ 0.05).The frequencies of genotypes CC,CG and GG were 77.62％ (163/210),20.48％ (43/210) and 1.90％ (4/210) in the case group,and 86.85％ (185/213),13.15％ (28/213) and 0(0/213) in the control group,with significant difference between the 2 groups (x2=8.54,P ＜ 0.05).Patients with rs2607775 GC genotype were associated with a significantly increased risk of pancreatic cancer compared with patients with rs2607775 CC genotype (adjusted OR =1.81,95％ CI:1.06-3.10,P ＜ 0.05).Patients with rs2607775 GC + GG genotype were associated with a significantly increased risk of pancreatic cancer compared with patients with rs2607775 CC (adjusted OR =1.98,95％ CI:1.16-3.36,P ＜ 0.05).The ratio of patients in the case group who smoked cigarettes ≥ 17 pack years was 25.24％ (53/210),which was significantly higher than 13.15 ％ (28/213) of the control group (x2 =11.37,P ＜ 0.05).The results of univariate analysis showed that patients who smoked cigarettes ≥ 17 pack years had higher risk of getting pancreatic cancer (adjusted OR =2.82,95％ CI:1.27-6.29,P ＜ 0.05).Patients who smoked cigarettes ≥ 17 pack years and with rs2607775 CC also had higher risk of getting pancreatic cancer (adjusted OR =2.87,95％ CI:1.18-6.99,P ＜0.05).No significant gene-environment interaction was observed between rs2607775 GC + GG and smoking ≥ 17 pack years (adjusted OR =3.65,95％ CI:0.67-20.03,P ＞ 0.05).Conclusions The polymorphisms of XPC rs2607775 may play a role in the onset of pancreatic cancer.Patients who smoke cigarettes ≥ 17 pack years are more easily to have pancreatic cancer.There is no interaction between smoking and XPC rs2607775 in influencing the progression of pancreatic cancer.