Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Objective To prepare a nano drug(PFOB@Lip-MMC)with liposome as the carrier,liquid perfluorooc-tyl bromide(PFOB)as core and mitomycin C(MMC)loading on the liposome shell and study its inhibitory effect on the proliferation of human pterygium fibroblasts(HPFs).Methods The thin film dispersion-hydration ultrasonic method was used to prepare PFOB@Lip-MMC and detect its physical and chemical properties.Cell Counting Kit-8,Cam-PI cell viability staining and flow cytometry were employed to detect the impact of different concentrations of PFOB@Lip-MMC on the via-bility of HPFs.DiI fluorescence labeled PFOB@Lip-MMC was used to observe the permeability of the nano drug to HPFs under a laser confocal microscope.After establishing HPF inflammatory cell models,they were divided into the control group(with sterile phosphate-buffered saline solution added),PFOB@Lip group(with PFOB@Lip added),MMC group(with MMC added),PFOB@Lip-MMC group(with PFOB@Lip-MMC added)and normal group(with fresh culture medi-um added)according to the experimental requirements.After co-incubation for 24 h,flow cytometer was used to detect the apoptosis rate of inflammatory cells,and the gene expression levels of interleukin(IL)-1β,prostaglandin E2(PGE2),tumor necrosis factor(TNF)-α and vascular endothelial growth factor(VEGF)in cells were analyzed by PCR.Results The average particle size and Zeta potential of PFOB@Lip-MMC were(103.45±2.17)nm and(27.34±1.03)mV,respec-tively,and its entrapped efficiency and drug loading rate were(72.85±3.28)％and(34.27±2.04)％,respectively.The sustained-release MMC of drug-loaded nanospheres reached(78.34±2.92)％in vitro in a 24-hour ocular surface environ-ment.The biological safety of PFOB@Lip-MMC significantly improved compared to MMC.In terms of the DiI fluorescence labeled PFOB@Lip-MMC,after co-incubation with inflammatory HPFs for 2 h,DiI fluorescence labeling was diffusely dis-tributed in the cytoplasm of inflammatory HPFs.The apoptosis rate of inflammatory HPFs in the PFOB@Lip-MMC group[(77.23±4.93)％]was significantly higher than that in the MMC group[(51.62±3.28)％].The PCR examination results showed that the gene transcription levels of IL-1 β,PGE2,TNF-α and VEGF in other groups were significantly reduced com-pared to the control group and PFOB@Lip group,with the most significant decrease in the PFOB@Lip-MMC group(all P＜0.05).Conclusion In this study,a novel nano drug(PFOB@LIP-MMC)that inhibited the proliferation of HPFs was successfully synthesized,and its cytotoxicity was significantly reduced compared to the original drugs.It has good bio-compatibility and anti-inflammatory effects,providing a new treatment approach for reducing the recurrence rate after pte-rygium surgery.

【Objective】 To investigate the correlation between heart rate variability (HRV) and the degree of nervousness before blood donation. 【Methods】 The psychological state of 253 blood donors before blood donation was assessed by the self-rating anxiety scale (SAS) and the degree of nervousness and their HRV were measured. The correlation between the SAS score, the degree of nervousness and the HRV parameters was analyzed, and the differences were compared among different types of donors by multivariate linear regression. 【Results】 A total of 247 blood donors were included in the study. Five HRV parameters in blood donors aged 18-24 were higher than in those aged 25 years and above(all P<0.05), and the anxiety level was higher in female donors(SAS score 41-46) than in males(SAS score 35-43)(P<0.001); the pre-donation SAS score was consistent with the assessment of the tension level (r=0.970, P<0.001); the pre-donation tension level and the SAS score were all significantly negatively correlated with VLF in HRV parameters(r=0.179, P=0.005), and the associations were independent of confounders such as age, body mass index and gender (P<0.05). 【Conclusion】 Compared with SAS and tension assessment, HRV is more objective, and can be used as one of the tests for assessing the tension level of blood donors. The inclusion of HRV in the routine screening of blood donors deserves further study for its application in assessing the anxiety level of blood donors before blood donation, identifying people prone to blood donation-related vasovagal reaction (DRVR), preventing and reducing the risk of DRVR, and improving the safety of blood donation.

Aim To study whether genetically predicted serum testosterone level is causally associated with sys-temic multisite atherosclerosis.Methods Based on two pooled databases of genome-wide association studies on testos-terone and atherosclerosis in European populations from two separate foreign countries,the causal effect between testosterone and atherosclerosis was assessed using two-sample Mendelian randomization analysis with data on testosterone-associated genetic variants as instrumental variables(Ⅳ),and by using the inverse-variance weighted(IVW)method,MR-Egger regression,and weighted median estimation.Results IVW results showed that genetically predicted circu-lating testosterone levels were negatively associated with the risk of peripheral atherosclerosis(OR=0.93,95％CI:0.86～1.00,P=0.01),and that elevated testosterone level may reduce the risk of developing peripheral atherosclerosis,while no evidence of a potential causal association was found with cerebral atherosclerosis,coronary atherosclerosis and other athero-sclerosis type(P＞O.05).Conclusion The final analysis showed a causal relationship between genetically predicted testosterone level and the risk of developing peripheral atherosclerosis,and the role of testosterone therapy in the prevention and treatment of atherosclerosis deserves attention and further study.

Objective To investigate the relationship between occupational noise exposure and glycated hemoglobin (HbA1c) levels, as well as prediabetes diagnosed by HbA1c. Methods A total of 1 181 workers from a cigarette factory were selected as the research subjects using a judgment sampling method. Workers were divided into control, low-level noise exposure and high-level noise exposure groups, consisting of 236, 359, and 586 individuals, respectively. The blood sample was collected for HbA1c test and occupation noise exposure intensity in workplace was detected by an area-sampling method. Results There were no statistical significant differences in HbA1c levels and prediabetes prevalence among the three groups of workers (all P>0.05). After adjusting for potential confounding factors such as years of service, gender, smoking, pack-years of smoking, alcohol consumption, and body mass index, multiple linear regression analysis showed that the high-level noise exposure group had higher HbA1c level than the control group (P<0.05). Multivariable logistic regression analysis results showed that the high-level noise exposure group had higher risk of prediabetes compared with the control group (P<0.05). Conclusion Occupational noise exposure could be a risk factor for the increased HbA1c levels and prediabetes incidence among the occupational population. More attention should be paid to the effects of occupational noise exposure on the HbA1c level in occupational health surveillance.

Objective:To analyze the duration of each phase of Unity MR-linac in clinical application, aiming to provide reference for clinical optimization of the process time.Methods:Clinical data of 55 patients treated with Unity MR-linac were retrospectively analyzed. All patients were divided into the adapt to position (ATP) and adapt to shape (ATS) groups according to the planning method. The duration of each phase in the treatment process, the name and the time of each sequence, the number of beams, segments and total monitor units (MUs) were recorded and compared between two groups. In addition, the set-up time was counted according to different treatment sites. The time of each sequence and set-up time were expressed as the median M (Q 1, Q 3), and the number of beams, segments and total MUs of each plan were described as the mean±SD. Results:42 patients underwent ATP with a total of 305 treatment sessions: setup time was 3(2, 5) min, MR scanning time was 5(4, 7) min, registration time was 3(3, 4) min, adaptive planning time was 8(4, 12) min, beam on time was 8(6, 11) min, and the total time was 30(25, 36) min. 13 patients received ATS with a total of 65 treatment sessions: setup time was 2(2, 3) min, MR scanning time was 7(5, 8) min, registration time was 4(3, 5) min, time of delineation of target and organs at risk was 12(9, 16) min, adaptive planning time was 11(10, 14) min, beam on time was 10(9, 11) min and the total time was 55(49, 61) min. The set-up time according to treatment sites was 4(2, 4) min in the head and neck, 2(2, 4) min in the chest, and 3(2, 5) min in the abdomen. The number of fields, segments and total MUs during ATP were 8.1±1.7, 49.9±31.2, 846.75±363.44 in the head and neck, 8.0±2.0, 60.7±13.3, 790.21±279.00 in the chest, and 9.7±2.0, 81.2±22.3, 2007.32±1053.81 in the abdomen, respectively. The number of fields, segments and total MUs during ATS in head and neck of one case were 13, 39, 993.07, and 9.5±1.5, 65.5±6.3, 2763.26±835.41 in the abdomen.Conclusions:MR-guided radiotherapy yields huge potential in clinical application. However, there is still much room for the improvement of shortening the process duration.

BACKGROUND: Due to the close relationship between the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and the physiological metabolism of bone tissue, human chitinase protein 40 (YKL-40) can regulate the PI3K/Akt signaling pathway related to breast cancer pathogenesis. Therefore, it is speculated that YKL-40 may regulate apoptosis in knee osteoarthritis (KOA) chondrocytes through the PI3K/Akt signaling pathway. OBJECTIVE: To study the mechanism by which YKL-40 regulates apoptosis in rabbit KOA chondrocyte s through the PI3K/Akt signaling pathway. METHODS: (1) New Zealand white rabbits were randomized into two groups. An animal model of KOA was made using anterior cruciate ligament dissection in the model group, whereas the right posterior knee joint capsule was cut but not dissected in the control group. Chondrocytes were extracted from the rabbits at 6 weeks after modeling. Hematoxylin-eosin staining and Mankin histological scoring of the cartilage tissue were performed, whereas immunohistochemical staining was used to detect type II collagen expression in chondrocytes. (2) The second-generation chondrocytes in the control group were used as normal control group, and those in the model group were further divided into four groups, followed by culture with high glucose DMEM medium containing 10% fetal bovine serum in KOA model group, 100 μg/L YKL-40 in KOA + YKL group, 50 µmol/L LY294002 in KOA + LY group, and 50 µmol/L LY294002 + 100 μg/L YKL-40 in KOA + YKL + LY group. The expression levels of collagen type II, matrix metalloproteinase 13, Akt, p-Akt, P53, Bcl-2 proteins in chondrocytes were detected by western blot. RESULTS AND CONCLUSION: Hematoxylin-eosin staining, Mankin histological score, and collagen type II immunohistochemical staining confirmed the successful construction of KOA animal model and successful chondrocyte culture. Compared with the normal control group, the collagen type II, Bcl-2, p-Akt protein expression levels in chondrocytes were significantly reduced in the KOA model group (P < 0.05), and matrix metalloproteinase 13 and P53 protein expression levels were significantly increased in the KOA model group (P < 0.05). Compared with the KOA model group, these indicators were significantly improved in the KOA + YKL group (P < 0.05), significantly worsened in the KOA + LY group (P < 0.05), and had no significant changes in the KOA + YKL + LY group (P > 0.05). However, there were significant differences between the KOA + YKL group and the KOA + LY group (P < 0.05). In addition, the expression level of p-Akt protein in chondrocytes had no difference among groups (P > 0.05). To conclude, YKL-40 can inhibit the apoptosis of KOA chondrocytes, accelerate the repair of KOA cartilage damage and delay the degeneration of cartilage by activating the PI3K/Akt signaling pathway. Therefore, YKL-40 can be used as a new target for clinical treatment of KOA.

Objective To investigate the effects of goal‐directed volume therapy (GDVT )on the intracranial pressure(ICP) and the balance of cerebral oxygen consumption and supply in selective neurosurgery. Methods Twenty‐four patients sched‐uled for intracranial tumor resection were randomly divided into 2 groups:conventional fluid management group (group C ,n=12) and GDVT group(group G ,n=12). Patients in group C received introperative fluid transfusion according to classical fluid management strategies while those in group G received GDT according to stroke volume variation (SVV) ,guided by Flotrac‐Vigileo system.Mean arterial pressure(MAP) ,heart rate(HR) ,cardiac index(CI) ,ICP ,SVV and jugular bulb oxygen saturation (SjvO2 )were recorded before the anesthesia induction(T1 ) ,at the moment of intubation(T2 ) ,at the moment of opening the hard meninges(T3),1hafteropeningthehardmeninges(T4),andattheendofthesurgery(T5).Thecerebraloxygenextractionra‐tio(CERO2 )was calculated. The duration of surgery ,crystalloid volume ,colloid volume ,blood transfusion volume ,urinary output and bleeding volume were recorded as well.Results The colloid transfusion volume ,the total fluid transfusion volume and uri‐nary output were significantly increased in group G when compared with those in group C (P<0.05).MAP ,CI ,and SjvO2 were much higher and CERO2 were much lower at T4 and T5 in group G than in group C(P<0.05). There was no significant differ‐ence in the ICP at each time point between groups G and C (P>0.05).Conclusion Goal‐directed fluid therapy optimizes the cardiac preload without increasing the ICP in selective neurosurgery ,and it also improves the balance of cerebral oxygen con‐sumption and supply.

Objective To investigate the distribution and drug resistance of pathogenic bacteria in patients with preg-nancy combined with urinary tract infection. Methods Mid-stream urine culture and drug susceptibility analysis were conducted on 552 patients with pregnancy combined with urinary tract infection. Results The top 3 pathogenic bacteria for pregnancy combined with urinary tract infection were escherichia coli, enterococcus faecium and acinetobacter bau-mannii. Escherichia coli remained low resistance rate to piperacillin-tazobactam (1.99%), imipenem (1.49%), amikacin (4.47%), cefperazone-sulbactam (2.98%) and macrodantin (3.98%), but high resistance rate to ciprofloxacin (73.13%) and levofloxacin (67.16%). Conclusion The spectrum and drug resistance rate of pathogenic bacteria in pregnancy combined with urinary tract infection are changing. The pathogenic bacteria in urine and their drug resistance should be closely monitored to provide reference for clinical drug use.