Bone is a dynamic tissue undergoing continuous regeneration and reconstruction， and its metabolic activities are mainly regulated by bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts. In addition， a variety of cells such as adipocytes， inflammatory cells， endothelial cells， and nerve cells can affect bone metabolism by changing the bone marrow microenvironment. The incidence of bone metabolic diseases caused by bone metabolism disorders is increasing with aging of the population. At present， the clinical treatment of bone metabolic diseases has the disadvantages of long cycle， high cost and many side effects. Therefore， there is an urgent need for safe and effective prevention and treatment drugs. Corylin is an isoflavonoid extracted from Psoraleae Fructus， which has a variety of pharmacological effects such as anti-inflammatory， anti-oxidation， anti-tumor， anti-atherosclerosis， attenuating obesity and improving insulin resistance. Studies have shown that corylin not only exerts osteoprotective effects by promoting osteoblast differentiation and inhibiting osteoclast differentiation， but also plays a positive role in bone metabolism by regulating lipid metabolism， inflammatory response， angiogenesis and anti-aging. The current review overviews the effects and mechanisms of corylin on regulating bone metabolism directly or indirectly， hoping to open up a new perspective for the prevention and treatment of osteoporosis， fracture， osteoarthritis and other related diseases.

Objective:To investigate the effect of sodium tanshinone ⅡA sulfonate (STS) on pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by H 2O 2 and its possible mechanism. Methods:From November 2021 to September 2022, HUVECs were used as the research subjects at Wuxi Ninth People’s Hospital. The experiment was divided into four groups: the blank control group (normal condition), blank + STS group, H 2O 2 group and H 2O 2 + STS group. When the cells reached 80% fusion, 500.00 μmol/L of H 2O 2 was added to H 2O 2 group and H 2O 2 + STS group for 3 hours, and then the medium containing 500.00 μmol/L H 2O 2 was removed. After that, the blank+ STS group and the H 2O 2+ STS group were each supplemented with 5.00 μg/ml of STS and co-cultured with HUVECs for 24 hours. CCK-8 was used to assess the impact of STS at various concentrations (0.00, 0.05, 0.50, 5.00, 50.00, 500.00 μg/ml) on the proliferation of HUVECs. DNA damage-positive cells were detected with TUNEL staining. The expression of NOD-like receptor protein 3 (NLRP3) was detected using real-time PCR (RT-PCR) to investigate the optimal concentration of pyroptosis induced by H 2O 2. A detection kit was used to measure the expression of reactive oxygen species (ROS) induced by H 2O 2. The effect of STS on the migration and tube formation of HUVECs during pyroptosis was examined using a cell scratch test and a matrix gel tube formation test. The expressions of NLRP3, caspase-1, interleukin-18, and interleukin-1β were detected using RT-PCR and Western blotting. Repeated measures ANOVA was used to compare the concentrations at different time points, t-tests were used to compare data between two groups, and one-way ANOVA was used to compare data between multiple groups. P<0.05 was considered statistically significant. Results:STS below 50.00 μg/ml had no effect on the proliferation of HUVECs, while 500.00 μmol/L H 2O 2 had the most significant effect on inducing pyroptosis in HUVECs. TUNEL staining showed that compared with the control group, the number of TUNEL-positive cells in H 2O 2 group was significantly increased, and the difference was statistically significant ( P<0.01). However, there was no significant difference in the number of TUNEL-positive cells in the H 2O 2+ STS group ( P>0.05). The results of ROS detection showed that compared with the H 2O 2 group, intracellular ROS levels in the H 2O 2+ STS group was significantly decreased, and the difference was statistically significant ( P<0.01). Cell scratch and tube formation in vitro experiments showed that compared with the control group, cell mobility and tube formation ability were significantly decreased in the H 2O 2 group (all P<0.01), and there was no statistical significance in the H 2O 2+ STS group (all P>0.05). RT-PCR and Western blotting results showed that, compared with the H 2O 2 group, the expression of pyroptosis-related factors in the H 2O 2+ STS group was significantly decreased (all P<0.05). Conclusion:STS can inhibit the excessive production of ROS, promote the cell migration and tubular formation of HUVECs after pyroptosis induction, and alleviate H 2O 2-induced pyroptosis of HUVECs, thereby promoting angiogenesis.

Objective To investigate the risk factors of in-hospital mortality and establish a risk prediction model for patients receiving venoarterial extracorporeal membrane oxygenation(VA-ECMO).Methods We retrospectively collected the data of 302 patients receiving VA-ECMO in ICU of 3 hospitals in Guangdong Province between January,2015 and January,2022 using a convenience sampling method.The patients were divided into a derivation cohort(201 cases)and a validation cohort(101 cases).Univariate and multivariate logistic regression analyses were used to analyze the risk factors for in-hospital death of these patients,based on which a risk prediction model was established in the form of a nomogram.The receiver operator characteristic(ROC)curve,calibration curve and clinical decision curve were used to evaluate the discrimination ability,calibration and clinical validity of this model.Results The in-hospital mortality risk prediction model was established based the risk factors including hypertension(OR=3.694,95%CI:1.582-8.621),continuous renal replacement therapy(OR=9.661,95%CI:4.103-22.745),elevated Na2+ level(OR=1.048,95%CI:1.003-1.095)and increased hemoglobin level(OR=0.987,95%CI:0.977-0.998).In the derivation cohort,the area under the ROC curve(AUC)of this model was 0.829(95%CI:0.770-0.889),greater than those of the 4 single factors(all AUC<0.800),APACHE Ⅱ Score(AUC=0.777,95%CI:0.714-0.840)and the SOFA Score(AUC=0.721,95%CI:0.647-0.796).The results of internal validation showed that the AUC of the model was 0.774(95%CI:0.679-0.869),and the goodness of fit test showed a good fitting of this model(χ2=4.629,P>0.05).Conclusion The risk prediction model for in-hospital mortality of patients on VA-ECMO has good differentiation,calibration and clinical effectiveness and outperforms the commonly used disease severity scoring system,and thus can be used for assessing disease severity and prognostic risk level in critically ill patients.

Objective To investigate the risk factors of in-hospital mortality and establish a risk prediction model for patients receiving venoarterial extracorporeal membrane oxygenation(VA-ECMO).Methods We retrospectively collected the data of 302 patients receiving VA-ECMO in ICU of 3 hospitals in Guangdong Province between January,2015 and January,2022 using a convenience sampling method.The patients were divided into a derivation cohort(201 cases)and a validation cohort(101 cases).Univariate and multivariate logistic regression analyses were used to analyze the risk factors for in-hospital death of these patients,based on which a risk prediction model was established in the form of a nomogram.The receiver operator characteristic(ROC)curve,calibration curve and clinical decision curve were used to evaluate the discrimination ability,calibration and clinical validity of this model.Results The in-hospital mortality risk prediction model was established based the risk factors including hypertension(OR=3.694,95%CI:1.582-8.621),continuous renal replacement therapy(OR=9.661,95%CI:4.103-22.745),elevated Na2+ level(OR=1.048,95%CI:1.003-1.095)and increased hemoglobin level(OR=0.987,95%CI:0.977-0.998).In the derivation cohort,the area under the ROC curve(AUC)of this model was 0.829(95%CI:0.770-0.889),greater than those of the 4 single factors(all AUC<0.800),APACHE Ⅱ Score(AUC=0.777,95%CI:0.714-0.840)and the SOFA Score(AUC=0.721,95%CI:0.647-0.796).The results of internal validation showed that the AUC of the model was 0.774(95%CI:0.679-0.869),and the goodness of fit test showed a good fitting of this model(χ2=4.629,P>0.05).Conclusion The risk prediction model for in-hospital mortality of patients on VA-ECMO has good differentiation,calibration and clinical effectiveness and outperforms the commonly used disease severity scoring system,and thus can be used for assessing disease severity and prognostic risk level in critically ill patients.

Objective:To investigate the effect of sodium tanshinone ⅡA sulfonate (STS) on pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by H 2O 2 and its possible mechanism. Methods:From November 2021 to September 2022, HUVECs were used as the research subjects at Wuxi Ninth People’s Hospital. The experiment was divided into four groups: the blank control group (normal condition), blank + STS group, H 2O 2 group and H 2O 2 + STS group. When the cells reached 80% fusion, 500.00 μmol/L of H 2O 2 was added to H 2O 2 group and H 2O 2 + STS group for 3 hours, and then the medium containing 500.00 μmol/L H 2O 2 was removed. After that, the blank+ STS group and the H 2O 2+ STS group were each supplemented with 5.00 μg/ml of STS and co-cultured with HUVECs for 24 hours. CCK-8 was used to assess the impact of STS at various concentrations (0.00, 0.05, 0.50, 5.00, 50.00, 500.00 μg/ml) on the proliferation of HUVECs. DNA damage-positive cells were detected with TUNEL staining. The expression of NOD-like receptor protein 3 (NLRP3) was detected using real-time PCR (RT-PCR) to investigate the optimal concentration of pyroptosis induced by H 2O 2. A detection kit was used to measure the expression of reactive oxygen species (ROS) induced by H 2O 2. The effect of STS on the migration and tube formation of HUVECs during pyroptosis was examined using a cell scratch test and a matrix gel tube formation test. The expressions of NLRP3, caspase-1, interleukin-18, and interleukin-1β were detected using RT-PCR and Western blotting. Repeated measures ANOVA was used to compare the concentrations at different time points, t-tests were used to compare data between two groups, and one-way ANOVA was used to compare data between multiple groups. P<0.05 was considered statistically significant. Results:STS below 50.00 μg/ml had no effect on the proliferation of HUVECs, while 500.00 μmol/L H 2O 2 had the most significant effect on inducing pyroptosis in HUVECs. TUNEL staining showed that compared with the control group, the number of TUNEL-positive cells in H 2O 2 group was significantly increased, and the difference was statistically significant ( P<0.01). However, there was no significant difference in the number of TUNEL-positive cells in the H 2O 2+ STS group ( P>0.05). The results of ROS detection showed that compared with the H 2O 2 group, intracellular ROS levels in the H 2O 2+ STS group was significantly decreased, and the difference was statistically significant ( P<0.01). Cell scratch and tube formation in vitro experiments showed that compared with the control group, cell mobility and tube formation ability were significantly decreased in the H 2O 2 group (all P<0.01), and there was no statistical significance in the H 2O 2+ STS group (all P>0.05). RT-PCR and Western blotting results showed that, compared with the H 2O 2 group, the expression of pyroptosis-related factors in the H 2O 2+ STS group was significantly decreased (all P<0.05). Conclusion:STS can inhibit the excessive production of ROS, promote the cell migration and tubular formation of HUVECs after pyroptosis induction, and alleviate H 2O 2-induced pyroptosis of HUVECs, thereby promoting angiogenesis.

Objective: To analyze the epidemiological characteristics and genetic characteristics of sapovirus (SaV) in a cluster of schools in Changzhou, so as to provide a reference for the treatment of clustered vomiting and diarrhea events in schools. Methods: The epidemiological data and laboratory test data of sapovirus clusters in Changzhou from 2019 to 2022 were collected and analyzed. Partial VP1 genes of SaV positive samples were amplified and sequenced for phylogenetic analysis. Results: A total of 8 cases of clusters of SaV epidemics were reported in Changzhou City from 2019 to 2022, with 118 reported cases. The total attack rate was 1.47%, and the median of the attack number was 15. There were 6 outbreaks in kindergartens and 2 outbreaks in primary schools, which were reported in the epidemic period from September to December. The main clinical manifestations were vomiting (113 cases, 95.76 %), abdominal pain (39 cases, 33.05%), and diarrhea (16 cases, 13.56%). Among the 8 outbreaks, 17 sample strains were successfully sequenced. 5 outbreaks were GII.3 , and the other 3 outbreaks were GI.1, GI .3 and GII.2. GI and GII were the main genotypes in this area, and GII .3 was the predominant strain. Conclusion SaV is an important pathogen in the clusters of vomiting and diarrhea in schools after the transmission of norovirus. Continuous surveillance of SaV should be carried out to further understand its epidemiological characteristics and genotype distribution, so as to provide scientific basis for the prevention and control of the epidemic in schools.

Objective:To explore the clinical value of 18F-fluoromisonidazole (FMISO) PET/CT hypoxia imaging in early response to heavy ion radiotherapy in patients with non-small cell lung cancer(NSCLC). Methods:From April 2018 to January 2021, the 18F-FMISO PET/CT images of 23 NSCLC patients (19 males, 4 females; age (64.9±10.3) years) who received heavy ion radiotherapy in Shanghai Proton and Heavy Ion Center were retrospectively analyzed. The evaluation parameters included tumor volume (TV), tumor to background ratio (TBR) before and after radiotherapy. Patients were divided into hypoxia group and non-hypoxia group with the baseline TBR value≥1.4 as hypoxia threshold. Wilcoxon signed rank test was used to compare the differences of TV and TBR before and after radiotherapy in 2 groups. Results:Of 23 NSCLC patients, 17 were hypoxia and 6 were non-hypoxia. Compared with the baseline, TV after the radiotherapy (59.44(22.86, 99.43) and 33.78(8.68, 54.44) cm 3; z=-3.05, P=0.002) and TBR after the radiotherapy (2.25(2.09, 2.82) and 1.42(1.24, 1.67); z=-3.39, P=0.001) of the hypoxia group were significantly lower, while TV (16.19(6.74, 36.52) and 8.59(4.38, 25.47) cm 3; z=-1.57, P=0.120) and TBR (1.19(1.05, 1.27) and 1.10 (0.97, 1.14); z=-1.89, P=0.060) of the non-hypoxia group decreased with no significant differences. Conclusions:Hypoxic NSCLC tumors are sensitive to heavy ion radiation. Compared with non-hypoxic tumors, hypoxic tumors respond more quickly, and a significant reduction in TV can be observed early after radiotherapy. Heavy ion radiation can significantly improve tumor hypoxia.

Objective:To evaluate clinical efficacy and safety of dupilumab in the treatment of moderate and severe atopic dermatitis (AD) in the elderly.Methods:An observational study was conducted, and a total of 42 elderly patients with moderate to severe AD were collected from Department of Dermatology, the First Affiliated Hospital of Soochow University from September 2021 to June 2022. These patients all received subcutaneous injection of dupilumab at an initial dose of 600 mg, followed by every-2-week injections at a dose of 300 mg, and the total course of treatment was 16 weeks. Clinical indicators, including eczema area and severity index (EASI) , numerical rating scale (NRS) , dermatology life quality index (DLQI) and investigator′s global assessment (IGA) , were recorded at weeks 0, 4, 8, 12 and 16, and the proportion of patients achieving more than 50% (EASI-50) and 75% (EASI-75) improvement in EASI scores were calculated; related laboratory indicators, including total serum immunoglobulin E (IgE) levels and eosinophil counts, were recorded at weeks 0, 4 and 16. During the treatment, adverse events were recorded. Statistical analysis was carried out by using chi-square test, one-way analysis of variance and t test with SPSS27 and GraphPad Prism 9.0 software. Results:Among the 42 patients, there were 25 males (59.5%) and 17 females (40.5%) , and their age was 71.82 ± 16.81 years. Among them, 17 patients (40.5%) presented with generalized eczema phenotype, 15 (35.7%) with flexor eczema phenotype, and 10 (23.8%) with prurigo nodularis phenotype. At weeks 4 and 16 after start of the treatment, the mean EASI score significantly decreased by 38.4% and 73.3% respectively, the mean NRS score significantly decreased by 53.0% and 77.4% respectively, and the mean DLQI score significantly decreased by 58.2% and 93.8% respectively compared with the corresponding scores before the treatment ( P < 0.05 or 0.001) . At weeks 4 and 16, the proportions of patients achieving an IGA score of 0 or 1 were 11.9% and 61.9% respectively, the proportions of patients achieving EASI-50 were 11.9% and 76.2% respectively, and the proportions of patients achieving EASI-75 were 2.4% and 57.1% respectively. Compared with the baseline levels, the mean total serum IgE level decreased by 23.1% and 38.2% at weeks 4 and 16 respectively ( P = 0.274, 0.395, respectively) , and the mean eosinophil count decreased by 24.4% and 37.5% at weeks 4 and 16 respectively ( P = 0.059, 0.735, respectively) . During the treatment, mild adverse events occurred in 6 (14.3%) patients, including conjunctivitis (3 cases) , fungal infection of the head and face (2 cases) , and psoriasiform dermatitis (1 case) , which subsided after symptomatic treatment. Conclusion:Dupilumab exhibited a rapid onset and marked efficacy in the treatment of moderate and severe AD in the elderly, with few and mild adverse events; however, some patients had not achieved EASI-50 or EASI-75 after 16-week treatment, and maintenance treatment was required.

Objective:To explore the applicability of the distance between facial marks classification in evaluating the severity of androgenic alopecia in men.Methods:From June to December 2019, the male Chinese with diagnosis of androgenic alopecia were evaluated in the specific clinic of alopecia of Hangzhou First People’s Hospital according to the distance between facial marks and BASP(basic and specific) classification. The classification based on the distance between facial marks measures the distance from the facial marks of the anterior hairline to the horizontal line of the eyebrow and the longest radius of hair loss in the hair rotation center, the hair recession of the patient’s forehead (F), temporal (M) and vertex (V) parts. The hair loss in each region is rated as 0-3 grade from light to heavy, and the final hair loss grading is expressed as FnMnVn, such as F1M2V0. The highest grade of hair loss in F, M and V is the overall grade of hair loss. SPSS 25.0 software was used to statistically analyze the general data of patients, and Kappa test was used to evaluate the consistency between the results of the distance classification and BASP classification. The repeatability of the distance classification was tested by the repetition rate of three hair loss specialists. When two or more specialists gave the same evaluation among the three hair loss specialists, the result was regarded as the standard result. The ease of use of the distance between facial marks classification was tested by the consistency rate between the grading results of two temporary trained general doctors and the standard results.Results:A total of 150 male patients, aged (32.8±7.9) years (19-58 years), were included, of which 99 patients were 24-35 years old, accounting for 66.00%. It can be observed that the onset age was earlier. As assessed in this classification, the patients who participated in the study were graded as mild in 65 cases(43.33%), severe in 58 cases(38.67%), and moderate, which was consistency with the results obtained by BASP classification ( κ=0.573, P<0.001). Three experienced alopecia specialists evaluated 150 patients through the distance between facial marks. The results showed that the repetition rates of frontal, temporal and parietal classification results were 98.00%(147/150), 97.33%(146/150) and 96.00%(144/150), respectively. The repetition rate of the final alopecia classification was 92.00%(138/150), and the repetition rate of the overall alopecia classification was 98.00%(147/150). The consistency rate between the overall alopecia classification results of two temporary trained general doctors and the standard results was 95.92%(141/147) and 96.60%(142/147), respectively, and the consistency rate of the other results was higher than 90.00% except for one general doctor who was 89.86%(124/138) in the final classification. Conclusion:The distance between facial marks classification is a comparatively accurate and easy-to-learn grading method designed for Chinese male androgenic hair loss patients based on objective measurement data.

Objective:To explore the applicability of the distance between facial marks classification in evaluating the severity of androgenic alopecia in men.Methods:From June to December 2019, the male Chinese with diagnosis of androgenic alopecia were evaluated in the specific clinic of alopecia of Hangzhou First People’s Hospital according to the distance between facial marks and BASP(basic and specific) classification. The classification based on the distance between facial marks measures the distance from the facial marks of the anterior hairline to the horizontal line of the eyebrow and the longest radius of hair loss in the hair rotation center, the hair recession of the patient’s forehead (F), temporal (M) and vertex (V) parts. The hair loss in each region is rated as 0-3 grade from light to heavy, and the final hair loss grading is expressed as FnMnVn, such as F1M2V0. The highest grade of hair loss in F, M and V is the overall grade of hair loss. SPSS 25.0 software was used to statistically analyze the general data of patients, and Kappa test was used to evaluate the consistency between the results of the distance classification and BASP classification. The repeatability of the distance classification was tested by the repetition rate of three hair loss specialists. When two or more specialists gave the same evaluation among the three hair loss specialists, the result was regarded as the standard result. The ease of use of the distance between facial marks classification was tested by the consistency rate between the grading results of two temporary trained general doctors and the standard results.Results:A total of 150 male patients, aged (32.8±7.9) years (19-58 years), were included, of which 99 patients were 24-35 years old, accounting for 66.00%. It can be observed that the onset age was earlier. As assessed in this classification, the patients who participated in the study were graded as mild in 65 cases(43.33%), severe in 58 cases(38.67%), and moderate, which was consistency with the results obtained by BASP classification ( κ=0.573, P<0.001). Three experienced alopecia specialists evaluated 150 patients through the distance between facial marks. The results showed that the repetition rates of frontal, temporal and parietal classification results were 98.00%(147/150), 97.33%(146/150) and 96.00%(144/150), respectively. The repetition rate of the final alopecia classification was 92.00%(138/150), and the repetition rate of the overall alopecia classification was 98.00%(147/150). The consistency rate between the overall alopecia classification results of two temporary trained general doctors and the standard results was 95.92%(141/147) and 96.60%(142/147), respectively, and the consistency rate of the other results was higher than 90.00% except for one general doctor who was 89.86%(124/138) in the final classification. Conclusion:The distance between facial marks classification is a comparatively accurate and easy-to-learn grading method designed for Chinese male androgenic hair loss patients based on objective measurement data.