This paper introduces the basic content of the compulsory national standard ISO 7439:2015 Copper-bearing contraceptive intrauterine devices--Requirements and tests standard analysis, and expounds the reasons for revising part of the standard during the conversion process according to the actual market situation of intrauterine contraceptive device containing copper in China. As a compulsory basic universal standard, it has a guiding significance for the manufacturers of IUD and can promote the improvement of product quality.
China ; Contraceptive Agents ; Copper ; Female ; Humans ; Intrauterine Devices

Objective To explore the activity and its possible neural mechanism of brain default mode network by using resting state functional magnetic resonance imaging (fMRI) in patients with mild cognitive impairment (MCI). Methods The 20 amnestic MCI patients and 25 healthy controls were included in this study, and all subjects underwent mini-mental state examination (MMSE), auditory verbal learning test (AVLT) and fMRI. The data were analyzed by amplitude of low frequency fluctuation (ALFF), and the enhanced and weakened regions of ALFF were observed and compared in both MCI patients and healthy controls. Results MMSE and AVLT tests showed that the memory function was seriously impaired in MCI patients compared with healthy controls, which is based on the short and long delayed episodic memory impairment (2.4±1.7 vs. 6.6±1.4, t=3.70, P＜0.01; 2.1±1.6 vs. 6.7±1.5, t=4.16, P＜0.01). The resting state fMRI showed that MCI patients had significant decreases of ALFF in hippocampal formation, parahippocampal cortex and lateral temporal cortex as compared with health controls (t=2.58, 2.43 and 1.75, all P＜0.01), which were closely relevant to the episodic memory. And they had significant increases in temporal-parietal joint and inferior parietal lobule (t=3.14 and 2.77, both P＜0.01). Conclusions MCI patients show significant decreased active intensity of some DMN nodes that is related to episodic memory in resting state. Increased active intensity in MCI patients would be some type of compensation.

Objective To optimize the formulation of metoprolol succinate ( MS) controlled release pellets by central composite design-response surface methodology .Methods MS sustained-release pellets were prepared using sugar pellet cores as starter beads , ethyl cellulose as coating materials and MS itself as a pore former .The formulation of MS sustained-release pellets was optimized by a central composite design with two factors at five levels .These two factors ( two independ-ent variables) were the pore former level and coating level , and the evaluated indexes ( namely dependent variables ) included the in vitro cumulative release percentages of MS at 1, 4, 8, 12 and 16 h, respectively.Results and Conclusion The results of mathematical equation fitting suggested that the second-order quadratic model was the optimal fitting equa-tion.According to the response surfaces , the optimum values at the pore former level and coating level weve ranged from 16%to 18%and 20% to 25%, respectively .The in vitro cumulative release percentage of MS from the pellets at 1 h reached 9.15%,which consequently eliminated the lag phase in the initial release period and exhibited a good sustained-release effect.Central composite design-response surface methodology can be applied to optimizing the coating formulation for MS sustained release pellets .

Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development. However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low immunogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions. This review aims to provide an up-to-date survey of the protein antigen-based vaccine formulation development, including the usage of immunostimulants and the optimization of vaccine delivery systems for intranasal and oral administrations.
Adjuvants, Immunologic ; pharmacology ; Administration, Intranasal ; Administration, Oral ; Antigens ; administration & dosage ; Drug Delivery Systems ; Humans ; Proteins ; administration & dosage ; Vaccination

Cancer is a highly aggressive and devastating disease, and impediments to a cure arise not just from cancer itself. Targeted therapies are difficult to achieve since the majority of cancers are more intricate than ever imagined. Mainstream methodologies including chemotherapy and radiotherapy as routine clinical regimens frequently fail, eventually leading to pathologies that are refractory and incurable. One major cause is the gradual to rapid repopulation of surviving cancer cells during intervals of multiple-dose administration. Novel stress-responsive molecular pathways are increasingly unmasked and show promise as emerging targets for advanced strategies that aim at both de novo and acquired resistance. We highlight recent data reporting that treatments particularly those genotoxic can induce highly conserved damage responses in non-cancerous constituents of the tumor microenvironment (TMEN). Master regulators, including but not limited to NF-kB and C/EBP-β, are implicated and their signal cascades culminate in a robust, chronic and genome-wide secretory program, forming an activated TMEN that releases a myriad of soluble factors. The damage-elicited but essentially off target and cell non-autonomous secretory phenotype of host stroma causes adverse consequences, among which is acquired resistance of cancer cells. Harnessing signals arising from the TMEN, a pathophysiological niche frequently damaged by medical interventions, has the potential to promote overall efficacy and improve clinical outcomes provided that appropriate actions are ingeniously integrated into contemporary therapies. Thereby, anticancer regimens should be well tuned to establish an innovative clinical avenue, and such advancement will allow future oncological treatments to be more specific, accurate, thorough and personalized.
Antineoplastic Agents ; therapeutic use ; CCAAT-Enhancer-Binding Protein-beta ; metabolism ; Humans ; Models, Biological ; Molecular Targeted Therapy ; methods ; trends ; NF-kappa B ; metabolism ; Neoplasms ; drug therapy ; metabolism ; Precision Medicine ; methods ; trends ; Signal Transduction ; drug effects ; Tumor Microenvironment ; drug effects

Objective:To analyze levels of carnitine and acylcarnitine in peripheral blood from septic infants and to investigate their changes and clinical values in sepsis in infants.Methods:This retrospective research involved 46 septic infants and 55 infants with noninfectious diseases who were hospitalized in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine.The clinical data were collected, the levels of carnitine and acylcarnitine in peripheral blood measured by tandem mass spectrometry were compared between the two groups, and the correlations of acylcarnitine levels with CRP and PCT were analyzed respectively.The septic infants were divided into two groups according to whether there were complications or not.The levels of free carnitine and acylcarnitine were compared between the two groups.Results:The levels of C6DC, C14: 1, C14OH and C16OH in peripheral blood were significantly higher in septic infants than those with noninfectious diseases( Z=-2.52、-2.05、-2.68、-2.82, all P<0.05). There is no significant difference in free carnitine level between two groups.These four acylcarnitine levels were positively correlated with PCT( r=0.44、0.44、0.40、0.49, all P<0.01). In septic group, the percent of infants with abnormal levels of C16OH was significantly higher in infants with complications than those without complications( χ2=4.51, P<0.05). Conclusion:The peripheral blood levels of several acylcarnitine elevate in septic infants, and have positive correlations with the strength of infection.Meanwhile, there is a higher proportion of having abnormal level of long chain acylcarnitine among infants with complications than those without complications.These results suggest that lipid metabolism has changed in septic infants and detecting acylcarnitine levels can be helpful in assessing the severity of sepsis.

Current studies have found that breast milk contains multiple growth factors with important biological functions, which play an important role in growth and immune regulation in early life.Epidermal growth factor(EGF)can promote the proliferation and differentiation of neonatal gastrointestinal mucosa epithelium, and can prevent the development of necrotizing colitis.Transforming growth factors(TGF)include transforming growth factor α and transforming growth factor β.Transforming growth factor α is related to gastrointestinal function, while transforming growth factor β promotes IgA production and has immunomodulatory effect.Hepatocyte growth factor(HGF)can not only promote gastrointestinal tract development as a nutritional factor, but also may work as an immune factor to enhance immunity.Neurotrophic factors promote early neurogenesis in the offspring of preeclampsia mothers.At the same time, the content of these growth factors in breast milk is related to the gestational age, region, diet and other factors.This article summarizes the research progress and clinical application value of these growth factors.

Objective:To investigate the efficacy and safety of dual wavelength pulsed dye laser combined with 30% supramolecular salicylic acid in the treatment of moderate and severe facial acne.Methods:Sixty patients with moderate and severe acne that visited the Dermatology Department of the First Affiliated Hospital of Chongqing Medical University from May 2020 to January 2021, were selected and randomly divided into observation group and control group, with 30 patients in each group. The observation group was given dual-wavelength pulsed dye laser combined with 30% supramolecular salicylic acid. 30% supramolecular salicylic acid was used once every two weeks, for a total of six times. Dual-wavelength pulsed dye laser was given once a month, for a total of three times. The control group was only given dual-wavelength pulsed dye laser, once a month, a total of three times.Results:Twenty-two cases (73.33%) in the observation group were effective, while 14 cases (46.67%) in the control group were effective. The efficacy of the observation group was better than that of the control group, and the difference was statistically significant (χ 2=4.44, P<0.05). There were no obvious adverse reactions in both groups. Conclusions:Dual-wavelength pulsed dye laser combined with 30% supramolecular salicylic acid is effective and safe in the treatment of moderate and severe facial acne, which is worth popularizing.

Objective To evaluate the clinical application value of transcatheter arterial methylene blue angiography in the localization of lower gastrointestinal arterial bleeding.Methods Ten patients with lower gastrointestinal arterial bleeding received interventional celiac artery angiography.After the bleeding responsible arteries were identified,a microcatheter was super-selectively placed in the bleeding responsible artery.During surgical procedure,the methylene blue solution was injected through the microcatheter to display the bleeding segment of the intestinal tract,providing precise localization of the bleeding intestinal segment for surgical resection.Results Transcatheter arterial methylene blue angiography could clearly display the bleeding segment of the intestinal tract.The bleeding segments of the intestinal tract in the 10 patients were quickly and accurately removed.After surgery,the gastrointestinal bleeding stopped,and no surgery-related complications occurred.Conclusion Transcatheter arterial methylene blue angiography can accurately detect the arterial bleeding segment of the lower gastrointestinal tract,which provides precise localization for quickly removing the bleeding segment of intestinal tract,therefor,this technique is worthy of widespread clinical application.(J Intervent Radiol,2023,32:1230-1232)

BACKGROUND:The application of miniscrew in adolescents is increasing day by day,but at present,there are few studies on bone mass in the external oblique line of the mandible in adolescents at home and abroad,and there is no systematic study on bone mass in the external oblique line of the mandible in adolescents in different growth and development periods. OBJECTIVE:To measure the bone mass in the external oblique line of the mandible in adolescents with different cervical vertebral bone ages using a cone-beam CT and to investigate the difference of bone mass in the external oblique line of the mandible in adolescents with different cervical vertebral bone ages and the correlation between bone mass in this area and the cervical vertebral bone age. METHODS:The cone-beam CT data of 105 adolescent patients before orthodontic treatment were collected and divided into CS3 group(n=24),CS4 group(n=26),CS5 group(n=29)and CS6 group(n=26)using the cervical vertebral maturation method.The adolescent mandibular buccal shelf was reconstructed by Mimics Medical 21.0 software.The width of buccal bone at 6 and 11 mm under the cemento-enamel junction and the bone height at 4 and 5 mm buccal to the cemento-enamel junction of right mandibular first and second molars were measured.The measured data were statistically analyzed.The measurement was made on four planes:plane 1 is the plane where the proximal mesial root of the mandibular right first molar is located;plane 2 is the plane where the distal mesial root of the mandibular right first molar is located;plane 3 is the plane where the proximal mesial root of the mandibular right second molar is located;and plane 4 is the plane where the distal mesial root of the mandibular right second molar is located. RESULTS AND CONCLUSION:In each group,the bone width on the buccal side of the external oblique line increased gradually from the first molar proximally to the second molar distally in adolescents,and the width of buccal bone at 6 and 11 mm under the cemento-enamel junction showed significant difference among different layers(P<0.05).The bone width of buccal bone at 11 mm under the cemento-enamel junction was greater than that at 6 mm.The bone height on the buccal side of the external oblique line increased gradually from the first molar proximally to the second molar distally in all four groups,and the bone height at 4 and 5 mm buccal to the cemento-enamel junction showed significant differences at different layers(P<0.05).The bone height at 4 mm buccal to the cemento-enamel junction was greater than that at 5 mm.On the fourth plane,the bone width at 11 mm buccal to the cemento-enamel junction was smaller in the CS3,CS4,and CS5 groups than in the CS6 group(P<0.05).On the third plane,the bone heights at 4 mm and 5 mm buccal to the cemento-enamel junction were smaller in the CS3 and CS4 groups than in the CS6 group(P<0.05).On the fourth plane,the bone height at 5 mm buccal to the cemento-enamel junction was smaller in the CS3 and CS4 groups than in the CS6 group(P<0.05).On the fourth plane,the bone height at 4 mm buccal to the cemento-enamel junction was smaller in the CS3 group than in the CS6 group(P<0.05).Spearman correlation analysis showed that there was no correlation between bone mass and the cervical vertebral bone age,except that there was a weak correlation between bone mass at some measurement sites and cervical vertebral bone age.To conclude,the bone mass in the external oblique area of the mandible in adolescents does not change significantly with the increase of cervical vertebral bone age.The buccal side of the mesial root and distal root of the mandibular second molar in the external oblique area of CS3-CS6 adolescents meets the requirement of bone mass for miniscrew implantation,which is a site available for miniscrew implantation.