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 explore the factors affecting changes of disc angle (ΔDA) during oblique lateral interbody fusion (OLIF) and establish a predictive model of ΔDA.Methods:This retrospective study included 119 patients with 174 segments undergoing OLIF procedures between July 2017 and August 2019 in Beijing Jishuitan Hospital. 45 males and 74 females with an average age of 62.1±9.8 years (33-86 years) were included. The lordotic cages were all 6 degrees. Radiographic parameters included preoperative and postoperative disc angle (DA), disc height (DH), ΔDA on flexion-extension views (ΔDA-FE), cage location and cage inclination. Pearson correlation coefficient and machine-learning techniques were utilized to identify factors related to ΔDA. Based on machine leaning techniques, ten-fold cross-validation for model training and validation were used to develop a predictive linear model for ΔDA.Results:The average ΔDA was 3.9°±4.8° with preoperative disc angle (preoperative DA) of 5.3°±5.0°. The average change of posterior DH (ΔPDH) was 3.1±2.1 mm with preoperative posterior DH of 6.6±1.9 mm. The average change of anterior DH was 6.1±3.2 mm. Pearson correlation analysis showed a significant negative correlation between ΔDA and preoperative DA ( r=-0.713, P<0.001), cage location ( r=-0.183, P=0.016), and ΔDA-FE ( r=-0.153, P=0.044). PDH changes were significantly negatively correlated with preoperative PDH ( r=-0.444, P<0.001) and positively correlated with cage location ( r=0.218, P=0.004). ΔDA was 10.8°±3.2° for negative preoperative DA (indicating kyphotic), 5.0°±3.7° for preoperative DA between 0° and 6°, and 1.0°±4.1° for preoperative DA>6°. A predictive model was developed using ten-fold cross-validation, resulting in the formula ΔDA=7.9°-0.8×preoperative DA ( R=0.707, MAE=2.837). Conclusion:Disc angle changes in OLIF primarily depend on the preoperative disc angle, secondly on cage location. The predicting model based on machine-learning techniques using preoperative disc angle facilitates preoperative planning for OLIF procedures.

Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.

Objective To compare the clinical outcomes between oblique lumbar interbody fusion(OLIF)and transforaminal lumbar interbody fusion(TLIF)for patients with degenerative spondylolisthesis during 2-year follow-ups.Methods Patients with symptomatic degenerative spondylolisthesis who underwent OLIF(46 cases)and TLIF(45 cases)between July 2017 and September 2020 with 2-year follow-ups were retrospectively reviewed.One level or two-level lumbar fusion were included.The primary outcomes were Visual Analogue Scale(VAS)and Oswestry Disability Index(ODI)at 2 years after surgery.The secondary outcomes included radiographic parameters,fusion rate,cage subsidence rate,and permanent nerve injury rate.Results No significantly different changes were noted in VAS-back[2(2,3)vs.2(2,2),P=0.943],VAS-leg[2(2,2)vs.2(2,2),P=0.988],and ODI[17％(10％,22％)vs.14％(10％,22％),P=0.417]between the OLIF group and the TLIF group,respectively.Greater restoration of disc height and segmental lordosis were obtained in the OLIF group[mean,(11.9±1.5)mm and 15.7°±7.2°]than in the TLIF group[mean,(9.2±2.0)mm and 12.5°±5.9°]at postoperative 2-year(P＜0.001 and P=0.029).The subsidence rate was lower in the OLIF group than in the TLIF group[19.6％(9/46)vs.40.0％(16/40),P=0.037].The fusion rates at postoperative 2-year were 93.5％(43/46)in the OLIF group and 87.5％(35/40)in the TLIF group,having no significant difference(P=0.562).The rates of permanent nerve injury were similar between the two groups[4.3％(2/46)vs.6.7％(3/45),P=0.980]at postoperative 2-year.Conclusion Short segment OLIF doesn't show better clinical outcomes and fusion rate than TLIF for degenerative spondylolisthesis,except for greater disc height restoration,greater segmental lordosis,and lower subsidence rate at postoperative 2-year.

The incidence and prevention of chronic non-communicable respiratory diseases represented by chronic obstructive pulmonary disease, bronchial asthma, and lung cancer, as well asrespiratory communicable diseases such as viral pneumonia and tuberculosis, are becoming increasingly severe and complex.Only by constructing the modern respiratory discipline system of pulmonary and critical care medicine (PCCM) and developing the standardized management of PCCM departments in the hospital, could we achieve the goal of establishing overall specialized capacity for respiratory diseases and improving the ability of disease prevention and treatment in China. This article introducedthe project design and practice exploration based on the standardized construction of PCCM department in hospital, in the context of the new pattern of modern respiratory discipline.It focused on project initiation and management, formulation of evaluation standards, identification process and grading, and phased effectiveness.It also discussed and analyzed the experience, enlightenment, existing problems and suggestions, which could provide reference and advance experience for innovation, governance and improvement of capacity building of respiratory specialty and high-quality development of other medical disciplines and specialties in China.

Atherosclerosis (AS) is a chronic and progressive arterial disease. It is an important cause of the occurrence and development of cardiovascular and cerebrovascular diseases. With the development of Traditional Chinese Medicine (TCM), TCM has many advantages in the therapy of AS, with less adverse reactions. Studies have shown that TCM can resist AS, and the mechanism mainly belongs to regulating lipid metabolism, anti-lipid peroxidation, anti-inflammation, anticoagulation, and protecting the structure and function of vascular endothelial cells. The mechanism of TCM for AS is warranted to be studied systematically, and the chemical components need to be further clarified.

Early childhood caries (ECC) is a significant chronic disease of childhood and a rising public health burden worldwide. ECC may cause a higher risk of new caries lesions in both primary and permanent dentition, affecting lifelong oral health. The occurrence of ECC has been closely related to the core microbiome change in the oral cavity, which may be influenced by diet habits, oral health management, fluoride use, and dental manipulations. So, it is essential to improve parental oral health and awareness of health care, to establish a dental home at the early stage of childhood, and make an individualized caries management plan. Dental interventions according to the minimally invasive concept should be carried out to treat dental caries. This expert consensus mainly discusses the etiology of ECC, caries-risk assessment of children, prevention and treatment plan of ECC, aiming to achieve lifelong oral health.
Child ; Child, Preschool ; Consensus ; Dental Caries/prevention & control* ; Dental Caries Susceptibility ; Humans ; Oral Health

Unhealthy diet, habits and drug abuse cause a variety of liver diseases, including steatohepatitis, liver fibrosis, liver cirrhosis and liver cancer, which seriously affect human health. The fabrication of highly simulated cell models in vitro is important in the treatment of liver diseases and drug development. This article summarized the common strategies for the construction of liver pathology models
Animals ; Disease Models, Animal ; Humans ; Liver ; Liver Cirrhosis/pathology* ; Liver Neoplasms/pathology* ; Non-alcoholic Fatty Liver Disease/pathology*

Objective:To evaluate the effect of oblique lateral interbody fusion (OLIF) combined with posterior fixation on segmental alignment in the treatment of degenerative spondylolisthesis (DS).Methods:The clinical data of 40 patients with DS who underwent OLIF combined with posterior fixation from July 2017 to December 2019 were retrospectively analyzed. There were 7 males and 33 females, aged 45-81 years, with an average age of 65.7±9.06 years. The total number of slip segments was 43, including 37 levels at L 4, 5, 5 levels at L 3, 4, and 1 level at L 2, 3. According to the decompression methods, the patients were divided into two groups. 22 patients with 23 levels were treated with direct decompression combined with laminectomy, and 18 patients with 20 levels were treated with indirect decompression without laminectomy. All patients underwent preoperative and intraoperative imaging examination. The disc height (DH), slip ratio (SR) and segmental lordosis (SL) were measured by preoperative CT and intraoperative fluoroscopy images. One-way repeated measures ANOVA was used to compare the radiographic parameters of the segmental alignment prior to cage implantation, following cage insertion and posterior fixation. Bonferroni test was used to compare the radiographic parameters between groups. Results:In the OLIF combined with the posterior fixation, there were statistically significant differences in the radiographic parameters of segmental alignment at different stages of operation [DH ( F=147.786, P<0.001) , SR ( F=83.754, P<0.001) , SL ( F=38.296, P<0.001) ]. DH increased from 7.99±1.39 mm to 11.69±1.72 mm ( P<0.001), SR decreased from 10.67%±4.67% to 8.66%±4.50% ( P=0.001) and SL increased from 7.26°±2.73° to 7.85°±2.30° ( P=0.425). After combined posterior fixation, SR further decreased from 8.66%±4.50% to 2.07%±4.00% ( P<0.001), SL further increased from 7.85°±2.30° to 10.72°±3.08° ( P<0.001), and DH had no significant change ( P=1.000). There was no significant difference in radiographic parameters between the direct decompression group and the indirect decompression group when prior to cage implantation, following cage insertion and following posterior fixation, respectively. Conclusion:OLIF combined with posterior fixation in the treatment of DS can further reduce the slip rate of patients with lumbar degenerative spondylolisthesis and increase the lordosis angle of the surgical segment. At the same time, the direct decompression combined with laminectomy has no significant effect on the segmental alignment.

Objective:To explore the effect of standardized pain assessment and peer education on self-efficacy, quality of life and pain control of cancer pain patients.Methods:From January 2019 to January 2020, convenience sampling was used to select 162 inpatient cancer patients admitted to Henan Cancer Hospital as the research object. Patients were divided into observation group ( n=82) and control group ( n=80) based on the odd and even numbers of the patient's ward end number. Patients in control group received regular health education and traditional pain assessment. Observation group carried out standardized pain assessment and peer education. We compared self-efficacy, quality of life, pain control of two groups of patients before and after intervention. Results:Before intervention, there was no statistically significant difference between the two groups of patients in terms of dimension scores and total scores of self-efficacy, quality of life ( P>0.05) . After intervention, dimension scores and total scores of self-efficacy and quality of life of cancer pain patients' pain between two groups were higher than those before intervention, and the differences were statistically significant ( P<0.01) . Dimension scores and total scores of self-efficacy and quality of life of cancer pain patients in observation group were higher than those in control group with statistical differences ( P<0.01) . The overall pain control effect of cancer pain patients in observation group was better than that in control group, and the difference was statistically significant ( Z=-3.721, P<0.01) . Conclusions:Standardized pain assessment and peer education applied to the pain management of cancer pain patients can effectively improve the pain control effect and self-efficacy as well as the quality of life.