Objective:Based on the questionnaire, to analyze the current status of children′s bone age assessment in China, especially the application of artificial intelligence (AI)-assisted bone age assessment system in the clinic.Methods:This was a cross-sectional study. The questionnaire was adapted by ourselves through the literature method and expert interview method, and the whole volume included 22 questions, which were released in the form of WeChat applet questionnaire star to the physician groups of several associations and entrusted to the radiology and paediatricians with senior titles. The results of the different types of questions were summarised and analyzed, and the chi-square test was used to compare the count data.Results:A total of 450 valid questionnaires were collected from 162 medical institutions in 26 provinces and cities and autonomous regions, of which 232 (51.6%) were from 87 (53.7%) tertiary hospitals and 218 (48.4%) from 75 (46.3%) secondary hospitals. Of the respondents, 115 (25.6%) were senior, 137 (30.4%) middle and 198 (44.0%) junior. Child bone age measurement was performed at 75.9% (66/87) of tertiary care organizations and 26.7% (20/75) of secondary care organizations, and the difference was statistically significant ( χ2=39.10, P<0.001). Left wrist radiographs were predominantly used for bone age assessment (76.0%, 123/162), with 72.8% (118/162) of sites using the ATLAS method of assessment and 17.9% (29/162) using the scoring method. A total of 98.4% (443/450) of respondents agreed that AI technology should be used to assist in bone age assessment, but only 9.3% (15/162) of healthcare organizations used AI-assisted technology. Conclusion:At present, bone age assessment is widely used in medical institutions, but there are problems with non-standardized examination methods, inconsistent assessment standards, and imprecise assessment results. Expectations for AI technology-assisted diagnosis exist among a wide range of physicians, but there are fewer users.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

Objective:To explore the optimal keV value of the virtual monoenergetic image (VMI) for displaying the osteosarcoma by using the dual-layer spectral detector CT and to evaluate its application value in determining the extent of intramedullary invasion of osteosarcoma.Methods:From August 2021 to August 2022, 57 patients with conventional osteosarcoma of long bone confirmed by biopsy in Beijing Jishuitan Hospital, Capital Medical University were retrospectively analyzed. All patients completed dual-layer spectral CT enhanced examination before limb salvage surgery, and tumor segment resection specimens were obtained after surgery. Conventional 120 kVp image and VMI of 40, 50, 60, 70 and 80 keV were obtained by spectral CT examination, and the CT values of tumors, image noise were measured and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the corresponding images were calculated. The objective evaluation among the six groups of images were assessed with the Friedman test, and then determined the optimal keV value. The maximum distance between the intramedullary boundary of osteosarcoma and the adjacent articular surfaces was measured on the best keV VMI and the tumor segment resection specimens. The Wilcoxon signed rank test was used to find the differences and the Spearman correlation analysis was used to evaluate the correlation between the distance measured from the best keV VMI and the specimens.Results:There were significant differences in CT value, image noise, SNR and CNR between 40-80 keV VMI and 120 kVp conventional CT images ( P<0.05). The CT value, SNR and CNR of 40 and 50 keV VMI were better than 120 kVp ( P<0.001). The 50 keV VMI was chosen as the best keV VMI to measure the intramedullary extent of osteosarcoma. The distance measured from 50 keV VMI was 103.9 (80.4, 131.4) mm, while the distance measured from specimens was 113.5 (94.0, 142.0) mm, and the difference was statistically significant ( Z=-5.76, P<0.001). The 50 keV VMI measurements in 51 patients were smaller than the gross specimens, which underestimated the tumor intramedullary extent, with the difference was 11.1 (6.6, 13.8) mm. The Spearman correlation analysis demonstrated a high positive correlation of distance measured on gross specimens with the 50 keV VMI ( r s=0.960, P<0.001). Conclusions:Dual-layer spectral detector CT with 50 keV VMI is the best image to show the limb osteosarcoma. Compared with gross specimens, the distance measured from CT underestimated the intramedullary invasion range of limb osteosarcoma about 10 mm, but the two show a good correlation.

One hundred eighty-four cases of awake craniotomy in Xijing Hospital from September 2010 to June 2019 were retrospectively included in the study.Patients were divided into Asleep-Awake-Asleep (AAA) group and monitored anesthesia care (MAC) group.In AAA group, general anesthesia was used in the early arousal period, sedatives and analgesics were stopped during the arousal period, and the bispectral index (BIS) value was maintained at 60-80 in the late arousal period.In MAC group, dexmedetomidine and remifentanil were intravenously infused in the early arousal period, and the BIS value was maintained at 60-80 in the late arousal pericd.Dexmedetomidine and remifentanil infused were reduced or stopped according to the Observer′s Assessment of Altertness/Sedation score during the arousal period, so that the patient could be awakened at any time, and the BIS value was maintained at 60-80 in the late arousal period.Compared with AAA group, the consumption of local anesthetic and remifentanil was significantly decreased, the operation and anesthesia time was shortened, the requirement for rescue analgesia was decreased, mean arterial pressure, end-tidal pressure of carbon dioxide (P ETCO 2) and partial pressure of arterial carbon dioxide (PaCO 2) were increased and partial pressure of arterial oxygen (PaO 2) was decreased after laryngeal mask insertion or sedation, and heart rate and PaO 2 were decreased, P ETCO 2 and PaCO 2 were increased after awakening in group MAC ( P<0.05). There were no significant differences in anesthesia failure rate in the awake craniotomy, incidence of adverse events during the arousal period, intraoperative incidence of tachycardia/bradycardia and hypertension/hypotension, Observer′s Assessment of Alertness/Sedation score during the arousal period, rate of postoperative visual analogue scale score>5 after surgery, postoperative requirement for rescue analgesia, neurological deficit rate and rehabilitation discharge rate between the two groups ( P>0.05). Compared with those after laryngeal mask insertion or after sedation, mean arterial pressure, heart rate, P ETCO 2 and PaCO 2 were significantly increased, and PaO 2 was decreased after awakening in AAA group ( P<0.05), and no statistically significant change was found in the parameters mentioned above after awakening in MAC group ( P>0.05). In summary, MAC shortens the operation and anesthesia time, no artificial airway is required, and it is suitable for the short time and minor operation.AAA has a better hemodynamics and oxygenation in the early arousal period, but the patient′s stress is more obvious after awakening, and effective prevention and intervention are needed.

Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Using different psoriasis animal models, we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PASI score and pathological injure evaluation. Mechanistically, IMMH002 regulated CD3 T lymphocytes re-distribution by inducing lymphocytes' homing, thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus. Our results suggest that the novel S1P agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment.

Objective:Aldo-keto reductase family 1 member B10 (AKR1B10) pathogenesis, early diagnosis and prognosis are closely related with hepatoma. Therefore, this study explores the effect and mechanism of AKR1B10 on cell cycle in hepatoma cells.Methods:HepG2 cells were infected with lentivirus LV-AKR1B10-shRNA or treated with epalrestat, an AKR1B10 inhibitor. The expression level of AKR1B10 was detected by Western blot assay and real-time fluorescence quantitative PCR (RT-qPCR). Decreased AKR1B10 activity was detected by reduced coenzyme II (NADPH) absorbance at 340 nm. The low expression of AKR1B10 and the effect of different concentrations of epalrestat on cell proliferation and cell cycle were detected by CCK-8 method and flow cytometry. The protein expression levels of p-rb, cyclin D1, E1, p27 in HepG2 cells were detected by Western blot. The mean of the two samples was tested using independent sample t-test.Results:AKR1B10 expression level in hepatoma cells was significantly increased compared to normal liver cells, and the relative expression level of AKR1B10 protein in HepG2 cells was 6.71 ± 1.11 ( P = 0.012). Epalrestat was significantly inhibited with the enzymatic activity of AKR1B10 in a dose-dependent manner. AKR1B10 gene in HepG2 cells was effectively silenced. HepG2 cells treated with different concentrations of epalrestat (AKR1B10 inhibitor) for 24, 48 and 72 h had inhibited cell proliferation, promoted G0/G1 cell cycle arrest, reduced the expression of p-Rb, cyclin D1, and cyclin E1 and increased the expression of cyclin dependent kinase inhibitor p27 expression. Conclusion:AKR1B10 inhibitory expression and activity can promote G0/G1 cell cycle arrest in HepG2 cells through the p27 / p-Rb pathway.

Objective: To investigate the inhibitory effect of AKR1B10 inhibitor combined with sorafenib on hepatocellular carcinoma (HCC) xenograft growth. Methods: HepG2 xenograft model was established in nude mice. The mice were then randomly divided into four groups: control group, epalrestat monotherapy group, sorafenib monotherapy group and combination treatment group. Tumor volume, tumor weight, T/C ratio and the change in body weight of nude mice in each group were compared to evaluate the curative effect. Immunohistochemistry staining was used to detect the expression of Ki-67 in tumor tissues to evaluate the proliferation status of tumor cells. One-way analysis of variance was used to compare the differences between the groups. Student’s t-test was used to test means of two groups and chi-square test was used for multiple samples. Results: The differences of the grafted tumor volume before and after treatment between the control group, epalrestat group, sorafenib group and combined therapy group was 238.940 ± 39.813, 124.991 ± 84.670, -26.111 ± 11.518, and -54.072 ± 17.673(mm³), respectively, (F = 37.048, P < 0.001). The tumor mass were 0.273 ± 0.140, 0.158 ± 0.078, 0.079 ± 0.054, 0.045 ± 0.024 (g), (F = 16.594, P < 0.001); T/C ratio were 100%, 57.9%, 28.9%, 16.5%, and Ki-67 positive rate were 23.295 ± 6.218, 13.503 ± 3.392, 7.325 ± 2.257, 4.664 ± 1.189 (%), (χ² = 822.203, P < 0.001) . The tumor volume (t = -3.579, P = 0.002) and Ki-67 positive rate (t = -10.003, P < 0.001) in epalrestat monotherapy group were significantly lower than control group. The tumor volume (t = 2.056, P = 0.025), tumor mass (t = 2.101, P = 0.043), and Ki-67 positive rate (t = -2.850, P = 0.005) in combination treatment group were significantly lower than sorafenib monotherapy group. Compared with the control group, the body weight of nude mice in the treatment group decreased to a certain extent, but there was no statistically significant difference between epalrestat monotherapy group and control group (t = -1.599, P = 0.262), and combined therapy and sorafenib monotherapy group (t = -0.051, P = 0.96). Conclusion AKR1B10 inhibitor enhanced the inhibitory effect of sorafenib on hepatocellular carcinoma xenograft.

Objective To analyze the prognosis ofⅠb2 andⅡa2 cervical squamous cancer without high risk factors treated with neo-adjuvant chemotherapy(NACT)and radical hysterectomy. Methods This retrospective study included patients with International Federation of Gynecology and Obstetrics (FIGO)stageⅠb2 andⅡa2 cervical squamous cancer without high risk factors who underwent platinum-based NACT followed by radical surgery from January 2008 to January 2015.The responses of NACT were observed and compared in their effect on postoperative pathologic risk factors. Kaplan-Meier method and Cox regression analysis were performed to analyze survival status. Results This study was recruited 282 patients with the average age of(44.4±6.7)years old.After NACT,42 patients achieved complete response [CR,14.9%(42/282)],while 138 patients achieved partial response[PR,48.9%(138/282)]and 102 stable disease [SD, 36.2%(102/282)]. The rate of pathologic diameter ≥4 cm, deep stromal invasion(DSI) positive and lymph-vascular space invasion(LVSI)positive rate decreased significantly in CR and PR group compared with SD group(P<0.05). The number of postoperative risk factors in CR, PR and SD groups varied significantly(χ 2=64.869, P=0.000). Besides,the rate of multiple intermediate risk factors was respectively 0 vs 13.8% vs 45.1%(χ2=7.107, P=0.008). The disease relapsed in 23 patients, and 12 died. On the whole series, 5-year overall survival rate was 91.7%, and 5-year recurrence-free survival rate was 88.9%. The rate of recurrence(P=0.002)and mortality(P=0.036)were higher in LVSI positive patients compared with LVSI negative. And the rate of recurrence was higher in patients with multiple intermediate risk factors,compared with no or one intermediate risk factors(P=0.002).Univariate analysis revealed that LVSI positive and multiple intermediate risk factors were the factors predicted recurrence and mortality(P<0.05), and no significance in age, stage, tumor grade, tumor diameter before or after NACT, response to NACT,or DSI positive factors(all P>0.05).The multivariate analysis showed that,the factor of primary tumor diameter≥6 cm(P=0.022)and multiple intermediate risk factors(P=0.001)were independent prognostic variables for recurrent-free survival.Besides,multiple intermediate risk factors was independent prognostic variable for overall survival(P=0.034). After surgery, 107 patients did not receive adjuvant therapy,while 175 patients received adjuvant therapy with 26 radiotherapy,46 chemotherapy and 103 concurrent radiochemotherapy.On survival analysis of postoperative adjuvant treatment,5-year recurrence-free survival rate of radiotherapy group was significantly lower in patients with the factor of SD response to NACT(P=0.011)and multiple intermediate risk factors(P=0.008), while overall no significance in overall survival rate(P>0.05).Conclusions NACT may be play beneficial role in relieving the status of intermediate risk factors for stage Ⅰb2 andⅡa2 cervical squamous cancer without high risk factors. The status of multiple intermediate risk factors is independent prognostic factors for recurrence and mortality. For patients with multiple intermediate risk factors, postoperative adjuvant chemotherapy or concurrent radiochemotherapy might be the better choice to prevent relapse.

Objective To explore the clinical efficacy of endovenous laser ablation (EVLA) of great saphenous vein combined with foam sclerotherapy in the treatment of variceal ulcer of lower extremities (VULE).Methods Data of 19 patients (20 affected limbs) with VULE were analyzed retrospectively.EVLA combined with foam sclerotherapy was performed,and the clinical effect was observed.Results The treatment was successfully performed in 19 patients (20 affected limbs).Diameters of the ulcer was (2.30 ± 1.61) cm before operation and (0.90± 0.32) cm 2 weeks after operation,respectively (t=10.53,P＜0.01),and the ulcers healed from 7 days to 3 months after the surgery in 20 patients without recurrence.Conclusion EVLA of great saphenous vein combined with foam sclerotherapy has good clinical efficacy.

Objective To observe the expression of protein AQP5 and CC16 in lung after hemorrhagic shock resuscitation in rats in order to explore the mechanism of acute lung injury.Methods Thirty-two healthy and clean male SD rats were randomly (random number) divided into two groups:control group and hemorrhagic shock resuscitation group (n =16 in each).Besides,each group was further divided into two subgroups according to the experiment done at 12 h and 24 h after hemorrhagic shock resuscitation (n =8).The hemorrhagic shock model was made by using Wiggers' modified method.Resuscitation was done by transfusing the autologous blood and the equal volume of Ringer's solution.Blood samples were obtained from abdominal aorta at each given interval to measure the level of plasma endotoxin,and assay the CC16 and AQP5 by using ELISA.After the rats were sacrificed,the left lung tissue was taken to measure lung water content and the dry/wet ratio,and to examine the levels of CC16 and AQP5 in lung tissue by immunohistochemical method.Results ①The level of plasma endotoxin in the experimental group was significantly higher than that in the control group (P ＜ 0.01).②The content of plasma CC16 in the experimental group was higher than that in the control group (P ＜ 0.05).③Compared with the control group,the content of pulmonary homogenate AQP5 in the experimental group was significantly lower (P ＜0.05).④The lung water content (the dry/wet ratio) of the experimental group was obviously higher than that of the control group (P ＜ 0.05).⑤Hislogogical observation with HE staining showed in the control group,the alveolar structure was complete,the alveolar sacs were clear,and the alveolar septum was intact;but in the experimental group,the alveolar septum was widened,and there were obvious hemorrhage and neutrophil infiltration in the alveolar space.⑥ The level of lung tissue CC16 in control group was significantly higher compared with experimental group (P ＜ 0.05).⑦ The level of lung tissue AQP5 was significantly higher in control group compared with experimental group (P ＜ 0.05).Conclusions The proteins of AQP5 and CC16 were involved in the process of acute lung injury after hemorrhagic shock resuscitation in rats,and their levels were positively correlated with length of time after hemorrhagic shock.