Objective:To provide a basis for improving the design and implementation of policies for ensuring the supply of pediatric drugs in China.Method:Based on the perspective of pharmaceutical enterprises,reviewed literature and conducts questionnaire surveys to identify the constraints in the development of pediatrict drugs throughout the entire drug lifecycle,and analyzes the constraints'concentration and urgency.Result:The main constraints include:difficulty in conducting clinical trials for children;the current registration and approval rules lack consideration for the specificity of pediatric drugs and specific requirements for application materials;lack of implementation rules and measures in the implementation process of incentive policies for pediatric drug production;The market interest mechanism of pediatric drugs is not yet perfect.Among them,research and development and payment for use are currently relatively concentrated issues.Discussion and suggestions:It is recommended that China fully utilize existing clinical trial data of pediatric and broaden sources,take multiple measures to increase investment in pediatric drug R&D;Develop special guidelines for pediatric drug application and encourage adult drug registration to submit pediatric research plans;Explore the optimization path of pediatrict drug production and supply based on typical cases;Provide more space for pediatric drugs in the rules of drug use and payment.

Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

The rare-earth-elements-doped upconversion nanoparticles NaYF4:Yb3+,Er3+were synthesized by solvothermal method,and NaYF4:Yb3+,Er3+@SiO2 were prepared by coating SiO2 on the surface of NaYF4:Yb3+,Er3+by inverse microemulsion method in this work.Based on the fluorescence quenching principle between NaYF4∶Yb3+,Er3+@SiO2 and SQA-Fe3+,a NaYF4∶Yb3+,Er3+@SiO2-SQA-Fe3+fluorescence nanosensor was constructed for detection of trace hydrogen peroxide(H2O2).Under optimal conditions,the linear range of this method for detecting H2O2 was 1.8?84.0 μmol/L,with detection limit(3σ)of 0.47 μmol/L.The recoveries of H2O2 spiked in milk were 98.4%?99.7%.This method could be used for detection of H2O2 residue in milk samples,with advantages such as low detection limit,good stability and strong anti-interference ability.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the clinical efficacy and surgical experience of modified posterior fossa decompression combined with dural expansion repair in the treatment of type Ⅰ Chiari malformation complicated with syringomyelia.Methods The clinical data of 47 patients with Chiari type Ⅰ malformation complicated with syringomyelia treated by modified posterior fossa decompression combined with dural expansion repair in our hospital were analyzed retrospectively.The changes of posterior cranial fossa volume,cerebellar tonsil and syringomyelia were evaluated by MRI after operation.The scores of Japanese Orthopaedic Association(JOA)were used to evaluate the improvement of neurological function,and the complications were recorded.Results All the 47 patients successfully completed modified posterior fossa decompression combined with dural expansion repair.The main postoperative complications were unilateral limb numbness,incision pain,fever,subcutaneous effusion and so on,all of which were cured after symptomatic treatment.During the follow-up period,the clinical symptoms and neurological function of the patients were improved in varying degrees,and there was no deterioration of neurological function or death cases.The JOA score of the patients 3 months after operation was(15.83±1.31),which was higher than that of(14.66±2.06)before operation,the difference was statistically significant(P<0.05).MRI showed the extent of syringomyelia was reduced or disap-peared 6 after surgery in all 47 patients.Conclusion Modified posterior fossa decompression combined with dural expansion repair for the treatment of type Ⅰ Chiari malformation complicated with syringomyelia can not only ensure the decompression effect,but also increase the support of the contents of the posterior fossa,effectively prevent postoperative local adhesions,and restore the normal physiological circulation of cerebrospinal fluid in the cisterna magnum,which is an effective treatment method for type Ⅰ Chiari malformation complicated with syringomyelia.

Humans ; Adult ; Serum Albumin, Human ; Consensus ; Cardiac Surgical Procedures ; Thoracic Surgery

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.
Humans ; Small Cell Lung Carcinoma/pathology* ; Lung Neoplasms/pathology* ; Radiotherapy, Intensity-Modulated/methods* ; Retrospective Studies ; Lung Injury ; Radiotherapy Dosage ; Radiation Injuries/epidemiology* ; Esophagitis/epidemiology* ; Risk Factors ; Pulmonary Disease, Chronic Obstructive/complications*

Objective: To evaluate the diagnostic value of serum human-βeta-defensin-1 level (HBD-1) for short-term (28-day) prognosis in patients with acute-on-chronic liver failure (ACLF). Methods: Fifty cases diagnosed with ACLF were selected. 20 cases with decompensated cirrhosis and 20 cases with compensated cirrhosis who were admitted at the same time were included. Age, gender, serum HBD-1 level, C-reactive protein (CRP), procalcitonin (PCT), neutrophil count/lymphocyte ratio (NLR), blood routine, coagulation function, liver function, kidney function, and other indicators from the three groups of patients were collected. Patients with ACLF were screened for indicators related to the short-term (28-day) prognosis. Patients were divided into an improvement group and a worsening group according to the 28-day disease outcome. The serum HBD-1 level and other above-mentioned indicators were compared between the two patient groups. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of serum HBD-1 levels for short-term prognosis in patients with ACLF. PCT, NLR, and prothrombin activity (PTA) application as a mono indicator and HBD-1 in combination with NLR, PCT, and PTA were compared to evaluate diagnostic efficacy for short-term prognosis in patients with ACLF. The intergroup mean of measurement data was determined using a t-test or analysis of variance. χ (2) test was used for comparison of count data. Spearman's rank correlation analysis was used for correlation analysis. Results: There was no statistically significant difference in age and gender among the three groups: ACLF, decompensated cirrhosis, and compensated cirrhosis (P > 0.05). The expression levels of serum HBD-1 in the ACLF group, decompensated cirrhosis group, and compensated cirrhosis group were (319.1 ± 44.4) ng/ml, (264.5 ± 46.5) ng/ml and (240.1 ± 35.4) ng/ml, respectively, while the ACLF group expression levels were significantly increased, with statistical significance (P < 0.01).The serum HBD-1 level was significantly higher in the ACLF worsening group (346.2 ± 43.6) ng/ml than that in the improvement group (308.5 ± 40.6) ng/ml, and the difference was statistically significant (P < 0.05). Correlation analysis showed that HBD-1, NLR, PCT, prothrombin time (PT), and international standardized ratio (INR) were negatively correlated with the 28-day disease outcome (improvement) of patients (P < 0.05). PTA was positively correlated with 28-day disease outcome (improvement) (P < 0.05). The area under the receiver operating characteristic curve (AUC) for evaluating HBD-1's diagnostic efficacy for short-term prognosis in patients with ACLF was 0.774, with a sensitivity of 0.750, a specificity of 0.786, and a cut-off point of 337.96 ng/ml. PCT, NLR, and PTA had greater diagnostic efficacy. HBD-1 combined with PTA had the highest diagnostic efficacy, with an AUC of 0.802, a sensitivity of 0.778, and a specificity of 0.786. The diagnostic efficacy of HBD-1+PCT, HBD-1+NLR and HBD-1, PCT, and NCR was superior to PTA mono. Conclusion: The serum HBD-1 level gradually increases with the aggravation of liver function injury and is negatively correlated with the short-term prognosis in patients with ACLF. Serum HBD-1 level has high sensitivity and specificity in predicting short-term prognosis in patients with ACLF, and its diagnostic efficacy is superior to that of PCT, NLR, and PTA. The combined application of HBD-1 and PTA has higher diagnostic efficacy; however, when the serum HBD-1 level is greater than 337.96ng/ml, it indicates poor prognosis in patients.
Humans ; Acute-On-Chronic Liver Failure/diagnosis* ; Prognosis ; Liver Cirrhosis ; C-Reactive Protein/analysis* ; ROC Curve ; Defensins ; Retrospective Studies

Objective: To analyze the impact of the sinonasal anatomic changes after endonasal endoscopic anterior skull base surgery on the nasal airflow and heating and humidification by computational fluid dynamics (CFD), and to explore the correlation between the postoperative CFD parameters and the subjective symptoms of the patients. Methods: The clinical data in the Rhinology Department of the First Affiliated Hospital of Zhengzhou University from 2016 to 2021 were retrospectively analyzed. The patients received the endoscopic resection of the anterior skull base tumor were selected as the case group, and the adults whose CT scans had no sinonasal abnormalities were chosen as the control group. The CFD simulation was performed on the sinonasal models after reconstructed from the patients' sinus CT images during the post-surgical follow-up. All the patients were asked to complete the Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) to assess the subjective symptoms. The comparison between two independent groups and the correlation analysis were carried out by using the Mann-Whitney U test and the Spearman correlation test in the SPSS 26.0 software. Results: Nineteen patients (including 8 males and 11 females, from 22 to 67 years old) in the case group and 2 patients (a male of 38 years old and a female of 45 years old) in the control group were enrolled in this study. After the anterior skull base surgery, the high-speed airflow moved to the upper part of the nasal cavity, and the lowest temperature shifted upwards on the choana. Comparing with the control group, the ratio of nasal mucosal surface area to nasal ventilation volume in the case group decreased [0.41 (0.40, 0.41) mm^-1 vs 0.32 (0.30, 0.38) mm^-1; Z=-2.04, P=0.041], the air flow in the upper and middle part of the nasal cavity increased [61.14 (59.78, 62.51)% vs 78.07 (76.22, 94.43)%; Z=-2.28, P=0.023], the nasal resistance decreased [0.024 (0.022, 0.026) Pa·s/ml vs 0.016 (0.009, 0.018) Pa·s/ml; Z=-2.29, P=0.022], the lowest temperature in the middle of the nasal cavity decreased [28.29 (27.23, 29.35)℃ vs 25.06 (24.07, 25.50)℃; Z=-2.28, P=0.023], the nasal heating efficiency decreased [98.74 (97.95, 99.52)% vs 82.16 (80.24, 86.91)%; Z=-2.28, P=0.023], the lowest relative humidity decreased [(79.62 (76.55, 82.69)% vs 73.28 (71.27, 75.05)%; Z=-2.28, P=0.023], and the nasal humidification efficiency decreased [99.50 (97.69, 101.30)% vs 86.09 (79.33, 87.16)%; Z=-2.28, P=0.023]. The ENS6Q total scores of all patients in the case group were less than 11 points. There was a moderate negative correlation between the proportion of the inferior airflow in the post-surgical nasal cavity negatively and the ENS6Q total scores (r_s=-0.50, P=0.029). Conclusions: The sinonasal anatomic changes after the endoscopic anterior skull base surgery alter the nasal airflow patterns, reducing the efficiency of nasal heating and humidification. However, the post-surgical occurrence tendency of the empty nose syndrome is weak.
Adult ; Humans ; Male ; Female ; Young Adult ; Middle Aged ; Aged ; Retrospective Studies ; Hydrodynamics ; Air Conditioning ; Nose ; Nasal Cavity ; Skull Base/surgery*

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens