In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the in vitro biological activity of teduglutide based on HTRF, after optimizing experimental conditions and methodological verification. We also carried out relative potency detection of teduglutide pharmaceutical products using this method. The result showed that there was a quantitative-efficient relationship between the teduglutide activity and cAMP contents in GLP-2R-HEK293 cells, which conformed to four-parameter model. Method verification results of five concentrations of teduglutide (64%, 80%, 100%, 125% and 156%) met the requirements of the General Rules of Chinese Pharmacopoeia, 2020 edition, Volume IV (9401). We then analyzed the relative potency of three batches of teduglutide drug substances and three batches of drug products. The linearity, regression and parallelism of the obtained curves all fit the system suitability requirements. The relative potency of six batches of teduglutide was from 83% to 105%. In summary, the biological activity detection method established in this study was accurate, precise, simple and time-saving, which can be used for quality control of teduglutide pharmaceutical products.

Aim To explore the protective effect of an-thocyanin B2(PCB2)on hydrogen peroxide(H2O2)induced oxidative damage and apoptosis in human oli-godendrocytes(MO3.13)and the underlying mecha-nism.Methods The optimal concentration of H2O2 and PCB2 for action was screened,and divided into normal group,PCB2 group(100 mg·L-1 PCB2 treat-ment for 24 hours),H2 O2 model group(500 μmol·L-1 H2O2 treatment for 24 hours),and H2O2+PCB2 group(500 μmol·L-1 H2O2 and 100 mg·L-1 PCB2 co-treated for 24 hours).FRAP method was used to detect the antioxidant capacity of PCB2;CCK-8 meth-od was used to detect the survival rate of cells in each group,while LDH method was used to assess cytotoxic-ity.Microenzyme-linked immunosorbent assay and ELISA were used to examine the levels of LDH,NO,H2O2,as well as the activities of CAT and SOD in each group of cells.Immunofluorescence and Western blot were used to detect the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4 in each group of cells.FerroOrange fluorescent probe was used to de-tect the intracellular content of ferrous ions(Fe2+).Results H2O2 could induce MO3.13 oxidative dam-age and lead to cell ferroptosis,while PCB2 could alle-viate MO3.13 oxidative damage and ferroptosis.Com-pared with the H2O2 model group,PCB2 intervention could significantly increase LDH content in MO3.13,reduce NO and H2O2 content,and improve SOD and CAT activity,and up-regulate the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4.Conclusion PCB2 can enhance cellular antioxidant capacity and alleviate H2O2 induced MO3.13 oxidative damage through the NRF2/HO-1/xCT/GPX4 axis.

AIM To evaluate the quality of Yanyangke Mixture.METHODS The HPLC fingerprints were established,after which cluster analysis,principal component analysis and partial least squares discriminant analysis were performed.The contents of liquiritin,rosmarinic acid,sheganoside,irisgenin,honokiol,monoammonium glycyrrhizinate,irisflorentin,isoliquiritin and magnolol were determined,the analysis was performed on a 35 ℃ thermostatic Agilent ZORBAX SB-C18 column(5 μm,250 mmx4.6 mm),with the mobile phase comprising of 0.1％phosphoric acid-acetonitrile flowing at 1 mL/min in a gradient elution manner,and multi-wavelength detection was adopted.RESULTS There were ten common peaks in the fingerprints for twelve batches of samples with the similarities of more than 0.9.Various batches of samples were clustered into three types,three principal components displayed the acumulative variance contribution rate of 87.448％,peaks 5、14(honokiol),3(liquiritin),11(monoammonium glycyrrhizinate)and 15(asarinin)were quality markers.Nine constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 98.5％-103.6％with the RSDs of 0.92％-1.7％.CONCLUSION This stable and reliable method can provide a basis for the quality control of Yanyangke Mixture.

Objective:To investigate the protective effects of a sunscreen lotion containing Calendula extracts on children′s skin against sun exposure, as well as to evaluate its safety and tolerability when applied to children.Methods:A single-center, randomized, split-body/face study was conducted on 200 healthy children aged 3 - < 18 years, who were enrolled from Beijing Children′s Hospital, Capital Medical University from July to August 2022. The participants were randomly and equally divided into Group A (the left side of the body/face topically treated with the test sunscreen, and the right side with the control sunscreen) and Group B (the right side of the body/face topically treated with the test sunscreen, and the left side with the control sunscreen) at a ratio of 1∶1. After applying the sunscreen, they were engaged in outdoor activities under sunlight. Skin tests were conducted on the temporal area, the extensor aspect of the upper arm and forearm before and after sun exposure. The test product was a mild sunscreen lotion containing Calendula extracts with the sun protection factor (SPF) being 50+ and the long-wave ultraviolet protection factor (PA) being +++, and the control product was a baby sunscreen containing licorice extracts (SPF35, PA++). Bilateral differential scales were used to assess clinical symptoms after sun exposure, erythema values to clinically evaluate erythema after sun exposure, and the multifunctional skin testing platform MPA10 to measure melanin and erythema values, stratum corneum hydration, and transepidermal water loss (TEWL) at the tested sites. Related adverse events were observed and recorded during the study. The paired t-test or Wilcoxon signed-rank test was used for the comparison of quantitative data, and chi-square test (Fisher′s exact test) for the comparison of count data. Results:Totally, 198 children completed the study and visits, including 100 males (50.5%) and 98 females (49.5%), aged from 3 to 17 years (8.11 ± 0.23 years), and there were 99 cases each in the Group A and Group B. The numbers of participants with more obvious sunburn symptoms after sun exposure in the 3 tested areas were all higher on the control side than on the test side (the temporal area: 11 cases vs. 4 cases; the extensor aspect of the upper arm: 16 cases vs. 2 cases; the extensor aspect of the forearm: 33 cases vs. 3 cases), with significant differences between the bilateral sides (all P<0.001). No significant differences were observed in the erythema values between the test side and control side in the 3 tested areas (all P > 0.05). In the extensor aspect of the upper arm and forearm, the difference in the melanin value before and after sun exposure was significantly smaller on the test side (3.57 ± 2.41, 1.74 ± 1.68, respectively) than on the control side (9.50 ± 2.21, 8.13 ± 1.87, respectively, both P < 0.001) ; in the temporal region and the extensor aspect of the upper arm and forearm, the difference in the stratum corneum hydration level before and after sun exposure was significantly greater on the test side (7.72[-2.19, 19.44], 9.56 ± 1.37, 9.05 ± 1.37, respectively) than on the control side (-3.25[-13.54, 9.94], 3.63 ± 1.32, 3.73 ± 1.31, respectively, all P < 0.001) in the temporal region and the extensor aspect of the upper arm and forearm. However, there were no significant differences in the changes in the erythema or TEWL values before and after sun exposure between the test side and control side in either of the 3 tested areas (all P > 0.05). During this study, 1 case (0.51%) experienced transient urticaria on the control side, and no serious adverse events occurred. Conclusion:The mild sunscreen lotion containing Calendula extracts demonstrated superior efficacy to the control product in improving skin symptoms after sun exposure such as hyperpigmentation among healthy children aged 3 - < 18 years, with good tolerability and a relatively low incidence of adverse reactions.

Objective:To investigate the cause of death, survival time, and risk factors in patients diagnosed with Alzheimer′s disease (AD) at memory clinic.Methods:The patients with AD were enrolled from the memory clinic at Huashan Hospital, Fudan University between August 2002 and December 2006. Baseline data were collected and 7 rounds of telephone follow-up visits were conducted to track clinical outcomes. For death cases, the date and cause of death were recorded. Patients were divided into several subgroups based on gender and baseline cognition [Mini-Mental State Examination (MMSE) score]. Kaplan-Meier analysis and Cox proportional hazards regression models were constructed to analyze the survival time of patients and identify the risk factors.Results:A total of 499 patients were enrolled, including 199 males and 300 females. The follow-up time was 5.5(3.4,7.4) years, with longest follow-up time of 19.3 years. The median survival time after symptom onset was 11.8 years (95% CI 10.2-13.4 years), which was 12.4 years (95% CI 11.2-13.5 years) in females, significantly longer than that in males (10.2 years, 95% CI 9.6-10.8 years, logrank test, P=0.010). The median survival time after diagnosis was 8.3 years (95% CI 7.3-9.4 years), which was 8.8 years (95% CI 6.9-10.6 years) for women, significantly longer than that for men (6.8 years, 95% CI 5.7-7.9 years, logrank test, P=0.001). Patients with baseline MMSE scores≥15 ( n=265) had a median survial of 11.4 years (95% CI 9.5-13.2 years), significantly longer than those with poorer cognitive function (baseline MMSE scores<15; n=234, 7.4 years, 95% CI 6.4-8.4 years, logrank test, P<0.001). Multivariable Cox proportional hazards regression analysis showed that aging ( HR=1.027, 95% CI 1.002-1.052, P=0.034), lower body mass index (BMI; HR=1.081, 95% CI 1.023-1.139, P=0.007), lower baseline MMSE score ( HR=1.056, 95% CI 1.026-1.086, P<0.001), diabetes ( HR=1.716, 95% CI 1.076-2.735, P=0.023), and history of falls ( HR=1.536,95% CI 1.007-2.341, P=0.046) were independent risk factors for death (all P<0.05). During the follow-up, 224 of the participants died. Except for 62 cases of unknown reason, the top 6 causes of death were pneumonia (39 cases, 24.1%), cerebrovascular disease (24 cases, 14.8%), circulatory system disease(21 cases, 13.0%), multi-organ failure (17 cases, 10.5%), tumor (13 cases, 8.0%), eating disorders and malnutrition (13 cases, 8.0%). Conclusions:In the current study, the median survival time after onset for patients with AD was 11.8 years; aging, lower BMI, lower baseline cognition, comorbidities, and history of falls were independent risk factors for death; pneumonia was the most common cause of death.

Chlorfenapyr,an emerging synthetic pesticide,has been linked to a growing number of poisoning incidents,attributed to heightened human exposure as its application becomes more widespread.However,the toxicokinetics and toxicology of chlorfenapyr remain incompletely understood.Research since the 1990s,including animal experiments,has illuminated the absorption,distribution,excretion,and metabolism of chlorfenapyr.Toxicological investigations have revealed that the primary toxicity of chlorfenapyr is the uncoupling of oxidative phosphorylation.Chlorfenapyr exposure in humans and other animals can lead to various toxic effects,including neurotoxicity,cardiotoxicity,skeletal muscle toxicity,genotoxicity,reproductive and developmental toxicity,renal toxicity,splenic toxicity,and hematotoxicity.This article presents a comprehensive review of the toxicokinetics and toxicology of chlorfenapyr,integrating data from animal experiments,human cell line studies,clinical reports,and human autopsy.Its objective is to raise clinical awareness regarding chlorfenapyr poisoning and offer valuable references for its treatment and management.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective To explore the machine learning model and risk factor analysis for hospital infection caused by carbapenem-resistant enterobacteriaceae(CRE).Methods The clinical data of totally 451 patients infected with extended-spectrum β-lactamases(ESBL)producing Enterobacteriaceae treated in the hospital from 2018 to 2022 were retrospectively collected.The patients were divided into CRE group(115 cases)and sensitive group(336 cases)according to the susceptibility of carbapenem.Four machine learning methods in-cluding Logistic regression analysis,random forest,support vector machine,and neural network were used to build prediction models and receiver operating characteristic curve was used to evaluate.Based on the predic-tion model with the best performance,risk factors for CRE infection were analyzed.Results Random forest model had the best performance,with the area under the curve of 0.952 3.The risk factors for predicting CRE infection by the random forest model included 15 clinical data items,namely fever for more than 3 days,cere-bral injury,drainage fluid sample,trunk surgery,first-level or special-level nursing,ICU treatment,procalcito-nin,anti-anaerobic bacteria,the use of third-generation cephalosporins,age,pre-albumin,creatinine,white blood cell count,and albumin.Conclusion The CRE prediction model developed in this study has good predic-tive value and the risk factors have guiding significance for the early prevention and treatment of CRE infec-tion in clinical practice.

Objective: To explore the relationship between the ratio of dietary vitamin A (VitA) to body weight and hypertension among children, so as to provide a reference for blood pressure control through dietary nutritional interventions and childhood hypertension prevention. Methods: Utilizing the baseline survey and followup sample data from the Healthy Children Cohort established in urban and rural areas of Chongqing from 2014 to 2019, structured quantitative dietary questionnaire and selfdesigned questionnaire were used to investigate the information of dietary intake and socioeconomic characteristics of 15 279 children, as well as blood pressure, height, weight measurement. The ratio of dietary VitA to body weight was divided into four groups based on quartiles [≤P25(Q1), >P25~P50(Q2), >P50~P75(Q3), >P75(Q4)]. Generalized linear regression models and Logistic regression models were used to analyze the correlation between ratio of dietary VitA to body weight with blood pressure levels and prevalence of hypertension. Results: The results of the 2014 baseline survey indicated that, after adjusting for confounding factors such as demographic indicators and nutritional intake, significant differences were observed in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) among different groups categorized by the ratio of dietary VitA to body weight (F=157.57, 44.71, 95.92, P<0.01). The baseline ratio of dietary VitA to body weight in children exhibited a negative correlation with DBP, SBP and MAP at baseline and in 2019[baseline: β(95%CI)=-0.65(-0.89--0.42), -0.22(-0.42--0.01), -0.36(-0.56--0.16); 2019: β(95%CI)=-0.77(-1.34--0.19), -0.62(-1.21--0.02), -0.77(-1.34--0.19), P＜0.05]. Compared to Q1 group, the risk of hypertension decreased among children in Q4 at baseline and followup in 2019 [OR(95%CI)=0.63(0.49-0.81), 0.18(0.08-0.42), P<0.01]. Conclusions The ratio of dietary VitA to body weight is significantly negatively correlated with blood pressure levels among children, and dietary VitA deficiency is an independent risk factor for hypertension among children. Measures should be taken to actively adjust childrens dietary nutrition and reduce the risk of childhood hypertension.

BACKGROUND:Currently,there is a lack of large sample studies to analyze the bone metabolism level of patients with femoral head necrosis of different etiologies and stages,which is not conducive to the development of better necrosis-promoting repair strategies. OBJECTIVE:To study the bone metabolism of patients with osteonecrosis of the femoral head with different etiologies and Association Research Circulation Osseous(ARCO)stages. METHODS:A retrospective study was performed on 401 patients diagnosed with osteonecrosis of the femoral head as the trial group,and 81 healthy subjects as the control group.The trial group could be divided into three groups according to different etiologies:steroid-induced osteonecrosis of the femoral head,alcoholic osteonecrosis of the femoral head and traumatic osteonecrosis of the femoral head,and were divided into stages Ⅱ/Ⅲ/Ⅳ according to different ARCO stages.Seven bone metabolism-related indicators of all subjects were collected,including bone metabolism-regulating hormone 25-hydroxyvitamin D and bone conversion markers:N-terminal propeptide of type Ⅰ procollagen,degradation product of type Ⅰ collagen,n-terminal middle molecular fragment of osteocalcin,general biochemical markers of bone metabolism:serum calcium,serum phosphorus,serum alkaline phosphatase.The bone metabolism levels of each group were compared and the independent factors associated with osteonecrosis of the femoral head were determined by binary Logistic regression analysis. RESULTS AND CONCLUSION:Compared with the control group,levels of degradation product of type Ⅰ collagen,N-terminal propeptide of type Ⅰ procollagen,n-terminal middle molecular fragment of osteocalcin,serum phosphorus and alkaline phosphatase in the trial group were significantly increased(all P＜0.05).Based on the presence or absence of the disease,according to binary Logistic regression analysis,degradation product of type Ⅰ collagen,N-terminal propeptide of type Ⅰ procollagen,and n-terminal middle molecular fragment of osteocalcin were independent factors associated with osteonecrosis of the femoral head.The levels of degradation product of type Ⅰ collagen and N-terminal propeptide of type Ⅰ procollagen in three groups of patients with different etiologies were higher than normal reference values.The bone metabolism-regulating hormone 25-hydroxyvitamin D and serum calcium in the alcoholic osteonecrosis of the femoral head group were higher than those in the other two groups(P＜0.05).The level of bone metabolism-regulating hormone 25-hydroxyvitamin D in steroid-induced and traumatic osteonecrosis of the femoral head groups was lower than the normal value.There were no significant differences in seven bone metabolism-related indicators in patients with ARCO stages Ⅱ,Ⅲ and Ⅳ osteonecrosis of the femoral head(all P＞0.05),but degradation product of type Ⅰ collagen and N-terminal propeptide of type Ⅰ procollagen in these three groups were higher than normal reference values.Bone metabolism-regulating hormone 25-hydroxyvitamin D in patients with ARCO stage Ⅱ and ARCO stage Ⅳ was lower than the normal reference value.It is concluded that the bone metabolism level of osteonecrosis of the femoral head patients was abnormal.The degradation product of type Ⅰ collagen and N-terminal propeptide of type Ⅰ procollagen of osteonecrosis of the femoral head patients with different etiologies and ARCO stages were all higher than the normal reference value,and they were in a state of high bone turnover.Degradation product of type Ⅰ collagen,N-terminal propeptide of type Ⅰ procollagen and n-terminal middle molecular fragment of osteocalcin may be risk factors for the pathogenesis of osteonecrosis of the femoral head.