Objective:To investigate the stability and feasibility of using absorbable screws during Bernese periacetabular osteotomy.Methods:A retrospective analysis was conducted on a 36 year-old woman diagnosed with developmental dysplasia of the hip, who had undergone Bernese periacetabular osteotomy. Finite element analysis was used to simulate the stability of the acetabulum under loads of 10%, 20%, 50%, and 100% of the patient's weight. The structural stiffness of the pelvis and the maximum equivalent stress on the absorbable screws were observed under different conditions, including whether the acetabular bone block and the ilium were in contact, whether 3 or 4 screws were used, and whether a graft (including fibular cortical bone and PEEK grafts) was used.Results:The structural stiffness of the pelvis fixed with four screws increased by 67%-94% compared to that with three screws. After using a graft, the structural stiffness of the pelvis increased by 50%-83%. As the load increased, the maximum equivalent stress on the screws also increased. When the acetabular bone block and the ilium had no contact, no graft was used, and only three screws were used for fixation, the maximum equivalent stress could reach 518.9 MPa, while this value dropped to 61% when four screws were used (318.7 MPa). When the acetabular bone block and the ilium were in contact, the maximum equivalent stress was about 12% of that when there was no contact, regardless of the number of screws used. When a cortical bone graft or a PEEK graft was used, the maximum equivalent stress could drop to 21%-26% of that without a graft. When the screw strength was 130 MPa, a load of 20% of body weight was applied, and only three screws were used without a graft, the equivalent stress could exceed the strength of the screw; if four screws were used, the equivalent stress was slightly higher than the strength of the screw when a load of 50% of body weight was applied. However, when a graft was used (either cortical bone or PEEK), even when a load of 100% of body weight was applied, the equivalent stress was slightly lower than the strength of the screw.Conclusion:Absorbable screws can provide sufficient stability for Bernese periacetabular osteotomy. The contact between the acetabular bone block and the ilium, an increase in the number of screws, and the use of grafts (cortical bone and PEEK grafts) can further improve stability. Therefore, absorbable screws have broad application prospects in Bernese periacetabular osteotomy.

Purpose: This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in metastatic breast cancer (MBC) patients. Materials and Methods: The meta-analysis of randomized clinical trials (RCTs) and propensity score matching of multicenter cohort study evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. This study is registered with PROSPERO: CRD42017071858 and ClinicalTrials.gov: NCT04258163. Results: A total of 2,867 patients from 15 RCTs and 760 patients from multicenter cohort were included. The results from meta-analysis showed that chemotherapy maintenance improved progression-free survival (PFS) (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.54 to 0.73; p < 0.001; moderate-quality evidence) and overall survival (OS) (HR, 0.87; 95% CI 0.78 to 0.97; p=0.016; high-quality evidence) than observation. In the cohort study, for hormone receptor–positive MBC patients, chemotherapy maintenance improved PFS (HR, 0.67; 95% CI, 0.52 to 0.85; p < 0.001) and OS (HR, 0.55; 95% CI 0.42 to 0.73; p < 0.001) compared with observation, and endocrine therapy maintenance also improved PFS (HR, 0.65; 95% CI, 0.53 to 0.80; p < 0.001) and OS (HR, 0.55; 95% CI, 0.44 to 0.69; p < 0.001). There were no differences between chemotherapy and endocrine therapy maintenance in PFS and OS (all p > 0.05). Regardless of the continuum or switch maintenance therapy, showed prolonged survival in MBC patients who were response to first-line treatment. Conclusion This study provided evidences for survival benefits of chemotherapy and endocrine therapy maintenance in MBC patients, and there was no difference efficacy between chemotherapy and endocrine therapy maintenance for hormone receptor–positive patients.

Objective:To prepare a phase-change lipid nanoparticle modified by tumor homing membrane-penetrating peptide (tLyP-1) and carrying paclitaxel (PTX) engineered by metal polyphenol network (TA-Fe 3+ ), and evaluate the therapeutic effects of tumor targeting, ultrasound/photoacoustic imaging and photothermal combined chemotherapy in vitro. Methods:Phase-change lipid nanoparticles (t-P@TFP) with TA-Fe 3+ engineered PTX mediated by tLyP-1 were prepared by solvent replacement method, thin film hydration method and double emulsification method. Its detection and characterization, in vitro targeting ability, photothermal conversion ability, in vitro photoacoustic and ultrasonic imaging ability, CCK-8 method, cell live and death double staining method and flow cytometry method were used to detect the safety of nanoparticles and the killing effects of different nanoparticles on 4T1 cells. Results:t-P@TFP nanoparticles were successfully prepared. Transmission electron microscopy showed that the nanoparticles were spherical with uniform shape and size, with a particle size of (209.8±1.56)nm and a potential of (-25.9±1.36)mV. Laser confocal scanning microscopy showed that t-P@TFP nanoparticles could gather around 4T1 cells in a targeted manner. It had an efficient photothermal conversion effect, and nanoparticles could quickly become microbubbles after being irradiated by near-infrared laser, which enhanced the in vitro ultrasonic imaging effect; The photoacoustic signal of nanoparticles increased with the increase of concentration. CCK-8 method, double staining of living and dead cells and flow cytometry showed that t-P@TFP combined photothermal chemotherapy had the best anti-tumor effect. Conclusions:t-P@TFP nanoparticles are successfully prepared. The nanoparticles have good targeting ability for photoacoustic and ultrasonic imaging and have good photothermal effect, killing breast cancer cells, which is expected to realize the integration of diagnosis and treatment.

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

Objective:To observe the efficacy and safety of mechanical ventilation combined with different doses of sildenafil in the treatment of persistent pulmonary hypertension of newborn (PPHN).Methods:A total of 160 children with PPHN admitted to Dezhou Maternal and Child Health Hospital from January 2018 to December 2019 were selected and divided into group A, B, C and D by random stratification, with 40 cases in each group. All the children in the group were actively corrected for acidosis, provided with intravenous nutrition support, warmth, anti-infection and other measures, and adopted ventilator to assist mechanical ventilation. Group A, B, and C were given different doses of sildenafil 0.5, 1.0, and 2.0 mg/(kg·time) respectively, while group D was not given sildenafil treatment, but only mechanical ventilation. Blood gas analysis indexes including partial arterial oxygenpressure (PaO 2), partial arterial carbon dioxide pressure (PaCO 2), saturationoxygen (SaO 2), and pulmonary artery pressure (SPAP), systemic blood pressure (SBP) of children were tested before the treatment and 72 h after the treatment. The treatment time, hospitalization time, hospitalization expenses and the incidence of adverse reactions of mechanical ventilation in 4 groups were recorded and compared. Results:The effective rate in the group A, B and C was higher than that in the group D: 80.0%(32/40), 85.0%(34/40), 87.5%(35/40) vs. 57.5%(23/40), the difference was statistically significant ( P<0.05). Before treatment, the levels of blood gas analysis indexes in 4 groups had no significant differences ( P>0.05). After treatment, the level of PaO 2 in the group A, B and C was significantly higher than that in the group D ( P<0.05), the level of PaCO 2 in the group B and C was significantly lower than that in group D ( P<0.05), and the level of SaO 2 in the group B and C was significantly higher than that in the group D ( P<0.05). After treatment, the level of SPAP in group B and C was significantly lower than that in the group D: (28.56 ± 3.93), (27.14 ± 3.32) mmHg(1 mmHg = 0.133 kPa) vs. (33.57 ± 4.68) mmHg, P<0.05, and the level of SBP in 4 groups had no significant difference ( P>0.05). The hospitalization time and mechanical ventilation time in group A, B and C were significantly shorter than those in group D ( P<0.05). No drug-related adverse reactions, pulmonary hemorrhage, hypotension, arrhythmia, pneumothorax and other complications occurred during the treatment in the 4 groups. Conclusions:Mechanical ventilation combined with sildenafil can significantly reduce pulmonary artery pressure and improve pulmonary oxygenation in children with PPHN. In the range of 0.5 - 1.0 mg/kg, the efficacy is more obvious when increasing the dose of sildenafil.

Objective:To explore the application effect of flipped classroom teaching method in musculoskeletal ultrasound teaching for standardized residency training of ultrasound department.Methods:In the study, 30 residents in ultrasound department of The Second Affiliated Hospital of Chongqing Medical University were collected and divided into control group ( n=15) and experimental group ( n=15). The control group was taught by traditional teaching method and the flipped teaching method was adopted in the experimental group. All residents were trained for 3 months. At the end of the training, theoretical test and operating skill test as well as the questionnaire survey were performed to evaluate the effects of these 2 teaching methods. SPSS 17.0 was used for t test and chi-square test. Results:The experimental group were superior to the control group in the aspects of the theoretical test scores, operating skill test scores, improving learning efficiency, building clinical thinking patterns, improving self-study ability, and there were significant differences. The satisfaction degree of teaching methods in the experiment group was higher than that in the control group, with significant differences ( P<0.001). Conclusion:Flipped classroom teaching method can improve the teaching outcomes and quality to ensure smooth completion of the teaching objectives.

Objective:To explore the changing characteristics of self-efficacy, social support, psychological stress in patients with osteoporotic vertebral compression fractures (OVCFs) receiving conservative treatment at different treatment stages and their correlations with the recovery of lower back function.Methods:A total of 116 patients with acute OVCFs who were admitted to the Affiliated Hospital of Medical School, Ningbo University were selected from January 2017 to May 2019. Oswestry Disability Index (ODI) Questionnaire, General Self Efficacy Scale (GSES) , Perceived Social Support Scale (PSSS) and Perceived Stress Scale (PSS) were used to assess the lower back function, self-efficacy, social support and psychological stress of OVCFs patients. Questionnaires were filled out during outpatient reexamination or in-home follow-up, and the evaluation time was at the time of treatment and 1, 3, 6, and 12 months after conservative treatment. Analysis of variance and SNK- q test were used to explore the characteristics of each score over time, and linear regression analysis was used to explore the effects of GSES, PSSS, and PSS on ODI. Results:With the prolongation of treatment time, ODI, GSES, PSSS and PSS scores of OVCFS patients under conservative treatment showed a downward trend, and the scores at 3, 6 and 12 months after treatment were lower than those at 1 month after conservative treatment ( P<0.05) . The scores at 6 and 12 months after conservative treatment were lower than those at 3 months after conservative treatment ( P<0.05) . The scores at 12 months after conservative treatment were lower than that those at 6 months after conservative treatment ( P<0.05) . GSES, PSSS (total score, in-family support, out-of-family support) and PSS were independent influencing factors of ODI at one month after treatment ( P<0.05) . GSES, PSSS (total score, in-family support) and PSS were the influencing factors of ODI at 3 months after treatment ( P<0.05) . Conclusions:The self-efficacy and social support of conservatively treated patients with OVCFs are positively correlated with their lower back function, while psychological stress will reduce lower back function of such patients. It is suggested to add these non-physical factors to the rehabilitation nursing model and take appropriate intervention measures.

Objective:To investigate the clinical application of cervix-uterine internal target volume (ITV) in volume-modulated arc therapy (VMAT) for cervical cancer under different bladder filling conditions, aiming to obtain more accurate planning target volume (PTV).Methods:Sixty-two patients with cervical cancer receiving radiotherapy rather than surgery were selected and randomly divided into the study ( n=31) and control groups ( n=31). In the study group, individualized ITV, PTV and PTV margin were obtained under three bladder filling status by localization CT scan to compare the VMAT. The target area and organs at risk (OARs) within the target area were statistically compared between two groups. The target missing rate in CBCT, adverse events and short-term efficacy of radiotherapy were analyzed in two groups. Results:There was no significant difference in the volume of target area and OARs in the target area between two groups (both P>0.05). In the study group, the target missing rate and target missing volume were significantly lower compared with those in the control group (both P<0.05). There was no significant difference in the incidence of acute radiation-induced adverse events between two groups ( P>0.05). The 1-, 2-year overall survival and progress-free survival did not significantly differ between two groups (all P>0.05). One patient in the study group had uterine recurrence and 2 cases in the control group. Conclusion:Application of individualized cervix-uterine ITV and PTV in definitive VMAT under different bladder filling conditions can improve the accuracy of target area contouring and improve the local control rate in cervical cancer patients.

Objective:To investigate changes in the expression of Cosmc and T-synthase in peripheral B lymphocytes and in serum levels of galactose-deficient IgA1 (Gd-IgA1) in patients with Henoch-Sch?nlein purpura (HSP) .Methods:From January to August 2014, 56 patients with HSP were collected from outpatient or inpatient department of dermatology and venereology in the Second Hospital of Hebei Medical University, and were divided into 4 groups, including skin type group (22 cases) , joint type group (9 cases) , abdominal type group (12 cases) and renal type group (13 cases) . Twenty healthy volunteers served as healthy controls. Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of Cosmc and T-synthase in peripheral B lymphocytes, and a lectin-based enzyme-linked immunosorbent assay (ELISA) to detect the serum level of Gd-IgA1. Comparisons among multiple groups were performed using one-way analysis of variance or Kruskal-Wallis H test, multiple comparisons were performed using least significant difference (LSD) - t test or Nemenyi test, and correlation analysis was performed using Spearman rank correlation analysis. Results:There was a significant difference in the duration from disease onset to the clinic visit ( χ2= 26.19, P < 0.05) among the skin type group (6.27 ± 3.09 d) , joint type group (5.56 ± 3.05 d) , abdominal type group (6.75 ± 3.75 d) , and renal type group (26.23 ± 14.12 d) , and the duration from disease onset to the clinic visit was significantly longer in the renal type group than in the other 3 groups (all P < 0.05) . The Cosmc mRNA expression significantly differed among the skin type group, joint type group, abdominal type group, renal type group and healthy control group (0.849 ± 0.239, 0.767 ± 0.181, 0.719 ± 0.183, 0.459 ± 0.121, 1.146 ± 0.232, F= 23.37, P < 0.05) , was significantly lower in the 4 patient groups than in the healthy control group ( P < 0.01) , and lower in the renal type group than in the other 3 patient groups (all P < 0.01) . There was no significant difference in the T-synthase mRNA expression in peripheral B lymphocytes among the patient groups and healthy control group ( F= 1.05, P > 0.05) . The serum level of Gd-IgA1 significantly differed among the skin type group, joint type group, abdominal type group, renal type group and healthy control group ( F= 7.06, P < 0.05) . Moreover, the Gd-IgA1 level was significantly higher in the patient groups than in the healthy control group (all P < 0.05) , and higher in the renal type group than in the other 3 patient groups (all P < 0.05) . The serum level of Gd-IgA1 in the HSP patients was significantly and negatively correlated with the mRNA expression of Cosmc ( rs=-0.50, P < 0.01) . Conclusion:Decreased mRNA expression of Cosmc and increased serum levels of Gd-IgA1 were observed in patients with HSP, and there was a negative correlation between the two indices.

Objective To explore the relationship between iodine and fluoride content in drinking water and the incidence of adult thyroid nodules in Cangzhou,Hebei.Methods According to the previous reports on iodine and fluoride levels in drinking water in Cangzhou,from November 2016 to January 2017,Cangzhou was divided into high iodine,low iodine,normal iodine and fluorine,low iodine and high fluorine,high iodine and high fluorine areas,and according to the different contents of iodine and fluorine in drinking water,high iodine and high fluorine area was further divided into high iodine and high fluorine 1 (iodine:743.30 μg/L,fluorine:4.27 mg/L),2 (iodine:119.31μg/L,fluorine:4.67 mg/L) and 3 (iodine:105.30 μg/L,fluorine:1.64 mg/L) subareas.Subjects who lived for 20 or more years and aged 30 or older,without serious disease and not taken iodized salt were selected.Palpation was used to examine the size,texture,mass,tenderness and mobility of the thyroid gland.The boundary,internal echo,blood flow and quantity of nodules were observed and recorded by color Doppler.Results The prevalence difference of thyroid nodules [36.8％ (629/1 710),32.8％ (636/1 938),25.1％ (427/1 700)] in high iodine,low iodine and normal iodine and fluorine areas was statistically significant (x2 =55.597,P ＜ 0.05).The prevalences of thyroid nodules in both high iodine and low iodine areas were higher than that of normal iodine and fluorine area (P＜ 0.016 7).The prevalence difference of thyroid nodules [43.3％ (749/1 730),39.8％ (712/1 790),34.9％ (623/1 785)] in high iodine and high fluorine 1,2 and 3 subareas was statistically significant(x2 =26.220,P ＜ 0.05).Compared with low iodine area,the prevalence of thyroid nodules [41.2％ (735/1 785)] in low iodine and high fluorine area was increased (x2 =6.288,P ＜ 0.05).Conclusions Both high iodine and low iodine can induce thyroid nodules.In water source areas with high iodine content,both high iodine and high fluorine are the factors inducing thyroid nodules.The prevalence of thyroid nodules in low iodine and high fluorine area is significantly higher than that of low iodine area.