Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.

Objective: To analyze the phenotype and genotype of two pedigrees with inherited fibrinogen (Fg) deficiency caused by two heterozygous mutations. We also preliminarily probed the molecular pathogenesis. Methods: The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and plasma fibrinogen activity (Fg∶C) of all family members (nine people across three generations and three people across two generations) were measured by the clotting method. Fibrinogen antigen (Fg:Ag) was measured by immunoturbidimetry. Direct DNA sequencing was performed to analyze all exons, flanking sequences, and mutated sites of FGA, FGB, and FGG for all members. Thrombin-catalyzed fibrinogen polymerization was performed. ClustalX 2.1 software was used to analyze the conservatism of the mutated sites. MutationTaster, PolyPhen-2, PROVEAN, SIFT, and LRT online bioinformatics software were applied to predict pathogenicity. Swiss PDB Viewer 4.0.1 was used to analyze the changes in protein spatial structure and molecular forces before and after mutation. Results: The Fg∶C of two probands decreased (1.28 g/L and 0.98 g/L, respectively). The Fg∶Ag of proband 1 was in the normal range of 2.20 g/L, while it was decreased to 1.01 g/L in proband 2. Through genetic analysis, we identified a heterozygous missense mutation (c.293C>A; p.BβAla98Asp) in exon 2 of proband 1 and a heterozygous nonsense mutation (c.1418C>G; p.BβSer473*) in exon 8 of proband 2. The conservatism analysis revealed that Ala98 and Ser473 presented different conservative states among homologous species. Online bioinformatics software predicted that p.BβAla98Asp and p.BβSer473* were pathogenic. Protein models demonstrated that the p.BβAla98Asp mutation influenced hydrogen bonds between amino acids, and the p.BβSer473* mutation resulted in protein truncation. Conclusion: The dysfibrinogenemia of proband 1 and the hypofibrinogenemia of proband 2 appeared to be related to the p.BβAla98Asp heterozygous missense mutation and the p.BβSer473* heterozygous nonsense mutation, respectively. This is the first ever report of these mutations.
Humans ; Afibrinogenemia/genetics* ; Codon, Nonsense ; Pedigree ; Phenotype ; Fibrinogen/genetics* ; Genotype

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To analyze the preoperative influencing factors of varus after Oxford unicompartmental knee arthroplasty. METHODS: A total of 660 patients (767 knees) undergoing Oxford unicompartmental knee arthroplasty in adult joint reconstruction surgery department of Beijing Jishuitan Hospital from January 2018 to December 2019 were retrospectively analyzed. Inclusive criteria: diagnosis was osteoarthritis, single compartment lesions in the medial side of the knee; preoperative flexion deformity was less than 10°, active range of motion was greater than 90°; preoperative X-ray full-length images of both lower limbs showed less than 15° varus (Noyes method); anterior cruciate ligament was well functioned, The cartilage of lateral compartment of knee joint was intact. EXCLUSION CRITERIA: combined with other inflammatory arthropathy; combined with extraarticular deformity; previous knee surgery history. The average age of the patients was (64.4±8.1) years, including 153 males and 497 females. The degree of post-operative varus was measured with Noyes method. The total patients were divided into varus group (Noyes≥3 °) and normal group (Noyes < 3 °). Gender, age, body mass index (BMI), range of motion (ROM), preoperative flexion deformity (FD), American Knee Society pain score (AKS) and American Knee Society function score (AKS function) were recorded. The standard anteroposterior and lateral X-ray films of knee joint and full-length lower extremity kinematic line films were taken by Sonialvision Safine Ⅱ (Shimadzu, Japan) multi-function digital tomography system. The image was measured by picture archiving and communication system (PACS). The following angles were measured preoperative Noyes angle, lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA) and joint line converge angle (JLCA) were measured and analyzed. RESULTS: Gender(P=0.346), operative side (P=0.619), age (P=0.746), BMI (P=0.142), preoperative ROM (P=0.102), preoperative knee pain score (P=0.131) and functional score (P=0.098) were not risk factors for postoperative varus. The influencing factors of postoperative varus were preoperative MPTA < 84 ° (P= 0.018, OR= 3.712, 95%CI: 1.250-11.027), preoperative Noyes > 5°(P=0.000, OR= 3.105, 95%CI: 1.835-5.254), preoperative FD > 5° (P= 0.001, OR=1.976, 95%CI: 1.326-3.234). Pre-operative LDFA (P=0.146) and preoperative JLCA (P= 0.709) had no significant effect on postoperative kinematic line. CONCLUSION Patients with severe preoperative varus, especially those with varus deformity mainly from the tibial side, and those with preoperative flexion deformity are more prone to get varus lower extremity kinematic line after Oxford unicompartmental knee arthroplasty.
Adult ; Aged ; Arthroplasty, Replacement, Knee ; Female ; Humans ; Knee Joint/surgery* ; Knee Prosthesis ; Male ; Middle Aged ; Multivariate Analysis ; Osteoarthritis, Knee/surgery* ; Range of Motion, Articular ; Retrospective Studies

Professor
Acupuncture ; Acupuncture Therapy ; Angina, Stable ; Combined Modality Therapy ; Humans ; Moxibustion

Background::Urbanization in China is rapidly proceeding, but rural-to-urban migration and its association with overweight and obesity is not well studied. This study aimed to explore the age at arrival, duration of migration, and the corresponding association with overweight/obesity in Yi migrants in China.Methods::A cross-sectional study was conducted in rural and urban areas in 2015 in Sichuan province, China. Demographic characteristics, lifestyle factors, and anthropometry were collected. General linear regression models were used to assess the effect of duration of migration (1-10, 11-20, 21-30, and >30 years) on body mass index (BMI). Multi-variable logistic regression was used to examine the association between duration of migration and overweight/obesity (BMI ≥ 25 kg/m 2). Results::A total of 3056 Yi people (1894 Yi farmers and 1162 Yi migrants) aged 20 to 80 years were enrolled. After adjusting for age, sex, and other potential confounders, Yi migrants had 1.71 kg/m 2 (95% confidence interval [CI]: 1.36-2.06) higher BMI and a 2.13-fold (95% CI: 1.71-2.65) higher risk of overweight/obesity than Yi farmers. In Yi migrants, stratified by age at arrival, no significant association between duration of migration and overweight/obesity was observed in those who were 0 to 20 years old at arrival. In comparison, in migrants >20 years old at arrival, compared with the reference group (1-10 years), long-term migration (>30 years) was found to be associated with overweight/obesity after adjustment (odds ratio: 1.85, 95% CI: 1.04-3.29). Conclusions::Yi migrants were observed to have greater risk of overweight/obesity than Yi farmers. In Yi migrants, the risk of overweight/obesity increased according to the duration of migration, especially in those who were older upon their arrival.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Objective:To explore the association between socioeconomic status (SES) and overweight/obesity in Yi people in Sichuan province.Methods:A cross-sectional study was conducted in Liangshan Yi Autonomous Prefecture in 2015. Stratified cluster sampling method was used to enroll Yi farmers and rural-to-urban Yi migrants aged 20-80 years. SES was measured by education level, personal annual income, and compound SES index. Unconditional logistic regression models were used to determine the association between SES and overweight/obesity (BMI≥24.0 kg/m 2). Results:1 894 Yi farmers and 1 162 rural-to urban migrants were included in the analysis. After adjustment for age, smoking, drinking and physical activity, compared with illiteracy, OR for farmer males with higher education level (primary or junior school, senior high school or higher) were 1.71 (95 %CI: 1.13-2.58) and 4.15 (95 %CI: 2.10-8.22). Compared with lower income group (<5 000 CNY/y), the higher income group had increased risk ( OR=1.66, 95 %CI: 1.12-2.44). For farmer males with medium and high SES level, the risk of overweight/obesity were 1.65 (95 %CI: 1.02-2.67) and 3.26 (95 %CI: 1.97-5.42) compared with low level of SES. For farmer females, the risk increased with the higher income, with OR as 1.49 (95 %CI: 1.10-2.02). Compared with low SES level, farmer females with medium level of SES was associated with 1.47 (95 %CI: 1.11-1.95) times higher risk of overweight/obesity. In Yi migrants, the association between SES and overweight/obesity was not found. Conclusion:Socioeconomic status was positively associated with overweight/obesity only in Yi farmers.

Background:The purpose of this study was to analyze cases of AO31-A2 intertrochanteric fractures (ITFs) and to identify the relationship between the loss of the posteromedial support and implant failure.Methods:Three hundred ninety-four patients who underwent operative treatment for ITF from January 2003 to December 2017 were enrolled.Focusing on posteromedial support,the A2 ITFs were divided into two groups,namely,those with (Group A,n =153) or without (Group B,n =241) posteromedial support post-operatively,and the failure rates were compared.Based on the final outcomes (failed or not),we allocated all of the patients into two groups:failed (Group C,n =66) and normal (Group D,n =328).We separately analyzed each dataset to identify the factors that exhibited statistically significant differences between the groups,In addition,a logistic regression was conducted to identify whether the loss of posteromedial support of A2 ITFs was an independent risk factor for fixation failure.The basic factors were age,sex,American Society of Anesthesiologists (ASA) score,side of affected limb,fixation method (intramedullary or extramedullary),time from injury to operation,blood loss,operative time and length of stay.Results:The failure rate of group B (58,24.07％) was significantly higher than that of group A (8,5.23％) (x2 =23.814,P ＜ 0.001).Regarding Groups C and D,the comparisons of the fixation method (P =0.005),operative time (P =0.001),blood loss (P =0.002)and length of stay (P =0.033) showed that the differences were significant.The logistic regression revealed that the loss of posteromedial support was an independent risk factor for implant failure (OR =5.986,95％ CI:2.667-13.432) (P ＜ 0.001).Conclusions:For AO31-A2 ITFs,the loss of posteromedial support was an independent risk factor for fixation failure.Therefore,posteromedial wall reconstruction might be necessary for the effective treatment of A2 fractures that lose posteromedial support.