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 analyze the changes in serum miR-205,miR-23b and miR-25 levels and their correlation with the prognosis of patients with different severities of sepsis.Methods A retrospective study was conducted in 86 patients with sepsis admitted to our hospital between September 2021 and September 2023.Based on the severity of illness,patients were divided into mild(52 cases)and severe(34 cases)groups.Eighty healthy individuals undergoing medical check-ups during the same period were selected as controls.The patients were follo wed-up for 28 days and were then categorized into a survival group(68 patients)and a death group(18 patients).Real-time polymerase chain reaction was used to detect the serum miR-205,miR-23b,and miR-25 levels in patients and analyze their corre-lation with prognosis.Multivariate Cox regression analysis was used to analyze the risk factors affecting patient prognosis.The diagnostic value of serum miR-205,miR-23b,and miR-25 levels in assessing sepsis and their predictive value for prognosis were analyzed using receiver operating characteristic curves.Results Serum miR-205,miR-23b,and miR-25 levels were significantly lower in the two groups of patients with sepsis than in the control group(P＜0.05),and were significantly higher in the survival group than in the death group(P＜0.05).Their levels negatively correlated with prognosis.Heart rate and APACHE Ⅱ score were risk factors for a poor prognosis of patients with sepsis,whereas high serum miR-205,miR-23b,and miR-25 levels were protective factors(P＜0.05).The areas under the curve(AUC)for individual serum miR-205,miR-23b,and miR-25 levels and their combination to assess sepsis were 0.794,0.786,0.768,and 0.926,respectively.The AUC for predicting poor prognosis for patients were 0.776,0.762,0.797,and 0.918,respectively.Conclusion Serum miR-205,miR-23b,and miR-25 levels were reduced in patients with sepsis,and were closely correlated with patient prognosis.Thus,they may serve as serological biomarkers for assessing disease and predicting prognosis.

OBJECTIVE To investigate the current status of hospital-associated infections,distribution of infection cases in departments,infection sites and pathogens so as to achieve the rational allocation of resources and provide data support for continuous improvement of medical quality.METHODS From 2019 to 2023,the relevant data in-cluding the departments of hospitalized patients with the infections,time of infections,infection sites and patho-gens were collected from all of the infection patients of Hohhot First Hospital by Xinglin nosocomial infection teal-time monitoring system and were statistically analyzed.RESULTS There were 1802 cases of hospital-associated infec-tions in total from 2019 to 2023,and the average incidence rate of infection was 1.18％.The average incidence of hospi-tal-associated infections exceeded 3％in 6 of 36 departments from 2019 to 2023(584 cases in total,accounting for 32.41％among all the cases),and the incidence of hospital-associated infections showed an upward trend in intensive care unit(ICU)(x2=4.125,P=0.042).The 3 major infection sites of the patients with hospital-associated infections were as follow:the patients with respiratory system infection accourted for 66.35％,the patients with urinary system infec-tions accounted for 19.39％,the patients with blood system infections 3.33％.Klebsiella pneumoniae,Escherichia coli and Acinetobacter baumannii ranked the top 3 species of pathogens causing the hospital-associated infection,accounting for 17.68％,12.25％and 11.33％,respectively.CONCLUSIONS The incidence of hospital-associated infections shows an upward trend in recent years.It is necessary to strengthen the comprehensive and meticulous management of the infec-tions and take full advantage of information surveillance data so as to further improve the medical quality and safety.

Objective To analyze the changes in serum miR-205,miR-23b and miR-25 levels and their correlation with the prognosis of patients with different severities of sepsis.Methods A retrospective study was conducted in 86 patients with sepsis admitted to our hospital between September 2021 and September 2023.Based on the severity of illness,patients were divided into mild(52 cases)and severe(34 cases)groups.Eighty healthy individuals undergoing medical check-ups during the same period were selected as controls.The patients were follo wed-up for 28 days and were then categorized into a survival group(68 patients)and a death group(18 patients).Real-time polymerase chain reaction was used to detect the serum miR-205,miR-23b,and miR-25 levels in patients and analyze their corre-lation with prognosis.Multivariate Cox regression analysis was used to analyze the risk factors affecting patient prognosis.The diagnostic value of serum miR-205,miR-23b,and miR-25 levels in assessing sepsis and their predictive value for prognosis were analyzed using receiver operating characteristic curves.Results Serum miR-205,miR-23b,and miR-25 levels were significantly lower in the two groups of patients with sepsis than in the control group(P＜0.05),and were significantly higher in the survival group than in the death group(P＜0.05).Their levels negatively correlated with prognosis.Heart rate and APACHE Ⅱ score were risk factors for a poor prognosis of patients with sepsis,whereas high serum miR-205,miR-23b,and miR-25 levels were protective factors(P＜0.05).The areas under the curve(AUC)for individual serum miR-205,miR-23b,and miR-25 levels and their combination to assess sepsis were 0.794,0.786,0.768,and 0.926,respectively.The AUC for predicting poor prognosis for patients were 0.776,0.762,0.797,and 0.918,respectively.Conclusion Serum miR-205,miR-23b,and miR-25 levels were reduced in patients with sepsis,and were closely correlated with patient prognosis.Thus,they may serve as serological biomarkers for assessing disease and predicting prognosis.

OBJECTIVE To investigate the current status of hospital-associated infections,distribution of infection cases in departments,infection sites and pathogens so as to achieve the rational allocation of resources and provide data support for continuous improvement of medical quality.METHODS From 2019 to 2023,the relevant data in-cluding the departments of hospitalized patients with the infections,time of infections,infection sites and patho-gens were collected from all of the infection patients of Hohhot First Hospital by Xinglin nosocomial infection teal-time monitoring system and were statistically analyzed.RESULTS There were 1802 cases of hospital-associated infec-tions in total from 2019 to 2023,and the average incidence rate of infection was 1.18％.The average incidence of hospi-tal-associated infections exceeded 3％in 6 of 36 departments from 2019 to 2023(584 cases in total,accounting for 32.41％among all the cases),and the incidence of hospital-associated infections showed an upward trend in intensive care unit(ICU)(x2=4.125,P=0.042).The 3 major infection sites of the patients with hospital-associated infections were as follow:the patients with respiratory system infection accourted for 66.35％,the patients with urinary system infec-tions accounted for 19.39％,the patients with blood system infections 3.33％.Klebsiella pneumoniae,Escherichia coli and Acinetobacter baumannii ranked the top 3 species of pathogens causing the hospital-associated infection,accounting for 17.68％,12.25％and 11.33％,respectively.CONCLUSIONS The incidence of hospital-associated infections shows an upward trend in recent years.It is necessary to strengthen the comprehensive and meticulous management of the infec-tions and take full advantage of information surveillance data so as to further improve the medical quality and safety.

With the development of the Scientific, Transparent and Applicable Rankings tool for clinical practice guidelines(STAR), the publication of evaluation and ranking for scientificity, transparency and applicability of Chinese guidelines and consensus published in the medical journals in 2021and 2022, as well as the publication of the STAR evaluation and ranking for some specialities, the STAR evaluation and ranking has received widespread attention in the medical community. In order to further enhance its scientificity and transparency, Methodology and Technology Specialization Committee of the STAR Working Group presents this article to introduce sample identification and speciality assignment in the evaluation and ranking process.

Objective·To investigate the effect of Astragali Radix on T lymphocyte subsets and cytokine expression in Hashimoto's thyroiditis patients with normal thyroid function.Methods·A total of 120 Hashimoto's thyroiditis patients with normal thyroid function and complete data were selected from January 2020 to December 2020 in Jinshan Branch of Shanghai Sixth People's Hospital.The patients were randomly divided into intervention group(n=60)and control group(n=60)by the method of random number table.The treatment plan of the control group was iodine appropriate state diet,and the intervention group was combined with oral Astragali Radix solution(150 mL per time,twice/d)on the basis of the treatment of the control group.The two groups were treated for 6 months.The changes in peripheral blood serum T lymphocyte subsets(CD3+,CD4+,CD8+,and CD4+/CD8+),cytokines[interleukin-2(IL-2),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)],hypersensitive C-reactive protein(hs-CRP),erythrocyte sedimentation rate(ESR),thyroid function,autoantibody,liver and kidney function,and other biochemical indexes were compared before and after treatment between the two groups.Adverse reactions were observed during the treatment.The factors influencing the change amplitude of thyroid peroxidase antibody(TPOAb)were analyzed by multifactor linear regression.Results·Finally,118 patients,with 59 cases in each group,were included in the study.After 6 months of treatment,the intervention group showed significant improvements in the proportions of CD4+ T cells,the ratio of CD4+/CD8+,and the levels of IL-2,TNF-α,IL-10,hs-CRP,ESR,TPOAb,and thyroglobulin antibody(TGAb)compared to the values before treatment and in the control group(P<0.05).There were no statistically significant differences on the above indicators before and after treatment in the control group(P>0.05).No serious adverse reactions were observed in the intervention group.Multiple linear regression analysis results showed that the use of Astragali Radix,increase of CD4+ level,increase of CD4+/CD8+ ratio,and decrease of hs-CRP level were influencing factors for the decrease of TPOAb level(β=-0.393,P=0.029;β=-0.513,P=0.010;β=-0.351,P= 0.035;β=0.434,P=0.023).Conclusion·Astragali Radix can improve the levels of CD4+ T cells,CD4+/CD8+ratio,IL-2,TNF-α,IL-6,and IL-10 in Hashimoto's thyroiditis patients with normal thyroid function,and it is safe to use.

Objective:To investigate the risk factors of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) complicated with pancreatogenic portal hypertension (PPH) and to establish a prediction model.Methods:From January 1, 2016 to December 31, 2022, a total of 1 095 patients diagnosed with MSAP or SAP at the First Affiliated Hospital of Kunming Medical University were enrolled and divided into PPH group (145 cases) and non-PPH group (950 cases) according to the presence or absence of concomitant PPH. The general data (gender, etiology of acute pancreatitis, days of hospitalization, etc.), complications (portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, etc.), laboratory indicators (albumin, D-dimer, etc.), and scores of modified computed tomography severity index (MCTSI) were collected in the two groups. The least absolute shrinkage and selection operator(LASSO) and multivariate logistic regression analysis were performed to analyze the independent risk factors of MSAP and SAP complicated with PPH, and the nomogram prediction model was established. The area under the curve of the receiver operating characteristic curve was calculated to evaluate the discrimination of the calibration curve and Hosmer-Lemeshow goodness of fit test were used to assess the predictive accuracy of the model, and clinical decision curve analysis (DCA) was used to evaluate the clinical practicability of the model.Results:The results of LASSO and multivariate logistic regression analysis showed that portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin were independent risk factors of MSAP and SAP complicated with PPH ( OR=7.013, 2.085, 1.846, 1.030, 1.235 and 0.955; 95% confidence interval 4.061 to 12.112, 1.255 to 3.463, 1.066 to 3.199, 1.013 to 1.047, 1.123 to 1.357 and 0.927 to 0.983; all P<0.05). The area under the curve of the model was 0.820 (95% confidence interval 0.780 to 0.859), the calibration curve was close to the reference curve, and the Hosmer-Lemeshow goodness-fit test showed that the model had a good fit ( χ2=9.82, P=0.278). The result of DCA indicated that the model had a high net benefit in a wide range of risk threshold (threshold probability 0.1 to 0.9), and had certain clinical practicability. Conclusions:Portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin are the independent risk factors of MSAP and SAP complicated with PPH. The established nomogram model has good differentiation, calibration and clinical practicability.

Objective:To investigate the risk factors of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) complicated with pancreatogenic portal hypertension (PPH) and to establish a prediction model.Methods:From January 1, 2016 to December 31, 2022, a total of 1 095 patients diagnosed with MSAP or SAP at the First Affiliated Hospital of Kunming Medical University were enrolled and divided into PPH group (145 cases) and non-PPH group (950 cases) according to the presence or absence of concomitant PPH. The general data (gender, etiology of acute pancreatitis, days of hospitalization, etc.), complications (portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, etc.), laboratory indicators (albumin, D-dimer, etc.), and scores of modified computed tomography severity index (MCTSI) were collected in the two groups. The least absolute shrinkage and selection operator(LASSO) and multivariate logistic regression analysis were performed to analyze the independent risk factors of MSAP and SAP complicated with PPH, and the nomogram prediction model was established. The area under the curve of the receiver operating characteristic curve was calculated to evaluate the discrimination of the calibration curve and Hosmer-Lemeshow goodness of fit test were used to assess the predictive accuracy of the model, and clinical decision curve analysis (DCA) was used to evaluate the clinical practicability of the model.Results:The results of LASSO and multivariate logistic regression analysis showed that portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin were independent risk factors of MSAP and SAP complicated with PPH ( OR=7.013, 2.085, 1.846, 1.030, 1.235 and 0.955; 95% confidence interval 4.061 to 12.112, 1.255 to 3.463, 1.066 to 3.199, 1.013 to 1.047, 1.123 to 1.357 and 0.927 to 0.983; all P<0.05). The area under the curve of the model was 0.820 (95% confidence interval 0.780 to 0.859), the calibration curve was close to the reference curve, and the Hosmer-Lemeshow goodness-fit test showed that the model had a good fit ( χ2=9.82, P=0.278). The result of DCA indicated that the model had a high net benefit in a wide range of risk threshold (threshold probability 0.1 to 0.9), and had certain clinical practicability. Conclusions:Portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin are the independent risk factors of MSAP and SAP complicated with PPH. The established nomogram model has good differentiation, calibration and clinical practicability.

Bevacizumab, an anti-VEGF monoclonal antibody, has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC (ns-NSCLC). However, the safety and efficacy of bevacizumab for elderly patients with advanced NSCLC require further investigation. Thus, 59 patients were included in the present retrospective study, 22 patients in the bevacizumab plus pemetrexed and platinum (B + PP) group, and 37 patients in the pemetrexed and platinum (PP) group. For the entire cohort of patients, the median OS was 33.3 months, and the 1-year and 2-year overall survival rates were 88.5% and 67.8%, respectively. The median OS and 1-year and 2-year OS rates were 20.5 months, 70.3% and 0%, respectively, in the B + PP group and 33.4 months, 97.0% and 89.4%, respectively, in the PP group (P < 0.001). The incidence of grade ⩾ 3 adverse events was higher in the B + PP group than in the PP group (27.3% vs. 10.8%, respectively; P = 0.204). Univariate and multivariate analyses suggested that the receipt of ⩾ 5 cycles of first-line chemotherapy was an independent favorable prognostic factor for OS, whereas the addition of bevacizumab was an unfavorable prognostic factor. With increased toxicities, the addition of bevacizumab to PP does not improve the overall survival of elderly patients with advanced ns-NSCLC.
Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Bevacizumab/adverse effects* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Lung Neoplasms/drug therapy* ; Pemetrexed/adverse effects* ; Platinum/therapeutic use* ; Retrospective Studies ; Treatment Outcome