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The pass rate of a test item often serves as an index of its difficulty. This posterior index, though easy to obtain and definite, is susceptible to students' learning level. It cannot play a leading role in designing test items. The present research tried to design a prior-to-test index of test item difficulty. According to the principles of cognitive task analysis, a frame and a procedure to be strictly executed were mapped out for the prior assessment of higher mathematics test items. Taking into account the characteristics of math problems, we designed such indexes as number of elements in a problem, element identification difficulty, number of principles used in answering, principle identification difficulty and cognitive load. The results show that prior difficulty is most significantly correlated with the pass rates of math test items. High correlation also exists among sub-indexes in assessment and among evaluators, indicating sufficient validity and reliability of the prior assessment method developed by the present reseach.

Xiaohui Tang,1,2 Qian Liang,1 Tao Li,1 Yetong Ouyang,1 Zhe Xue Huang,1 Xiaoshun Tang,1 Jiayi Jin,1 Lijia Yu,1 Xijin Wang1 1Department of Neurology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Neurology, Zhabei Central Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Xijin Wang, Department of Neurology, Shanghai Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Putuo District, Shanghai, 200065, People’s Republic of China, Tel +8613651627382, Email wangxijin2004@163.comPurpose: Impulse control disorders (ICDs) and excessive daytime sleepiness (EDS) are common symptoms in Parkinson’s disease (PD). Few longitudinal studies have focused on the association between EDS and ICDs. This longitudinal study aimed at assessing association between EDS and ICDs in PD.Patients and Methods: Patients without ICDs were incorporated from the Parkinson’s Progression Markers Initiative. All patients were followed until the onset of ICDs or the end of 4 years. A total of 260 PD patients were included. Univariable and multivariable logistic regression were used to explore association between EDS and ICDs.Results: The overall frequency of ICDs at the end of follow-up was 23.8% (62 patients). The mean duration from dopamine replacement therapy to develop ICDs was 3.30 ± 2.42 years. Patients with ICDs had significantly higher Epworth Sleepiness Scale (ESS) score (P = 0.002) and higher proportion of EDS (P = 0.030) when compared to patients without ICDs. The multivariable logistic regression analysis indicated that high ESS (OR = 2.01, 95% CI 1.01– 4.04, p = 0.049) score, high dopamine agonist equivalent daily dose (OR = 2.54, 95% CI 1.37– 4.71, p = 0.003), high Geriatric Depression Scale (OR = 2.33, 95% CI 1.27– 4.28, p = 0.006) score and postural instability (OR = 3.03, 95% CI 1.26– 7.29, p = 0.013) were associated with ICDs occurrence.Conclusion: Our results indicated that EDS acts as a risk for ICDs occurrence in PD. Clinicians should pay attention to EDS in clinical practice. This may be a promising new approach to better understand and therapy ICDs.Keywords: excessive daytime sleepiness, impulse control disorders, Parkinson’s disease, risk factors

The introduction of digital technologies into the learning process for medical university students represents a new paradigm in medical education since high level of criteria for assessing the quality of learning of a medical student require the application of modern technologies in training fundamental disciplines and, in particular, anatomy. Thanks to virtual technologies, conditions are created for modeling and integrating the student into conditions close to real ones, which increases the interest and involvement of students in the educational process and, as a result, a subjective improvement in the process of assimilation of the material. Traditional education based on dissection materials cannot fully provide for the massive training of students, as biological materials cannot be restored or preserved and are quickly damaged. 3D models are devoid of these limitations.Aim: to evaluate the effectiveness of digital dissection in the educational trajectory of clinical anatomy using interactive anatomical tables and the need of students for the active use of these aids.Materials and methods. Four groups of students were formed: three groups were studying the material using various anatomical tables and one group used the traditional method. To control the effectiveness of the educational process, before the start of training, entrance testing was conducted in all groups. At the end of classes on individual topics, participants completed exit testing, as well as a questionnaire.Results. The analysis of learning outcomes shows a significantly higher level of absorption of the material among students in groups where 3D anatomical models were used during classes. This indicates that students’ subjective experience of the learning process has improved due to their increased involvement in the class and their interest in innovative teaching methods.Conclusion. We plan to study learning outcomes in more detail to identify any differences in the formation of general and professional competencies among students. This information will help us make informed decisions about the widespread use of anatomical models in educational practice.

Introduction. The microbiota dynamics of the core biotopes during pregnancy are hardly studied, although changes in these compartments have an important role in both the functioning of the female organism and foetal development.Objective. To study the dynamics and interactions of changes in bladder, vaginal and bowel microbiota in healthy pregnant women over three trimesters (TRI-1, 2, 3).Materials & Methods. Study design: a single-centre comparative observational longitudinal study. Thirty out of first-time 220 pregnant women were selected for screening at the antenatal clinic from 2021 to 2022. All pregnant women underwent sampling at T-1, 2, 3: mid-stream bladder urine samples, posterior vaginal swabs and faecal masses were collected for culture study. After a special pre-culture preparation, samples were examined on an expanded set of nutrient media (n = 13) using special cultivation (aerobic-anaerobic) conditions. Based on the research results, identification frequencies (IDFs), microbial load values (MLVs) and microbial co-occurrence coefficients between the different biotopes were estimated.Results. Culture study revealed various bacteria in each biotope investigated during all TRIs. In the urine, aerobes and anaerobes were observed from TRI-1 to TRI-3 with different IDFs, but no taxa showed a stable IDFs. In the vagina, IDFs of bacteria were similar to urinary. The bowel microbiota was the most stable biotope remained almost unchanged during pregnancy. In the urine and vagina, mean MLVs of most aerobes and anaerobes did not change significantly throughout pregnancy. In the bowel, MLVs were consistently higher than in the urine and vaginal swabs. According to the co-occurrence analysis bladder-vagina and bladder-bowel biotopes showed significantly more interconnections between microorganisms in all TRIs.Conclusion. The observed microbiota structure during all TRIs is associated with uncomplicated gestation. These results will be valuable for studying changes of microbiota in complicated pregnancies.

Lai-Xi Zhao,1,* Qiong Sun,2,* Chong Wang,3,* Jia-Jia Liu,1 Xiao-Rong Yan,1 Meng-Ci Shao,1 Li Yu,3 Wen-Hua Xu,1 Rui Xu1 1College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, 230032, People’s Republic of China; 2Department of Stomatology, Anhui Province Direct Subordinate Hospital, Hefei, 230601, People’s Republic of China; 3Department of Microbiology and Parasitology, School of Basic Medical Sciences, Anhui Medical University, Anhui Province Key Laboratory of Zoonoses, The Provincial Key Laboratory of Zoonoses of High Institutions in Anhui, Hefei, Anhui Province, 230032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wen-Hua Xu; Rui Xu, Email xuwenhua@ahmu.edu.cn; dentistxr@126.comAbstract: Immunotherapies such as immune checkpoint blockade (ICB) therapy and chimeric antigen receptor T-cell (CAR-T) therapy have ushered in a new era of tumor treatment. However, most patients do not benefit from immunotherapy due to limitations such as narrow indications, low response rates, and high rates of adverse effects. Toxoplasma gondii (T. gondii), a specialized intracellular protozoan, can modulate host immune responses by inhibiting or stimulating cytokines. The ability of T. gondii to enhance an organism’s immune response was found to have a direct anti-tumor effect and enhance the sensitivity of patients with tumors to ICB therapy. However, the application of T. gondii for tumor therapy faces several challenges, such as biosafety concerns. Exosomes, a subtype of extracellular vesicle that contains active components such as proteins, nucleic acids, and lipids, have become effective therapeutic tools for various diseases, including tumors. Parasites, such as T. gondii, mediate the communication of pathogens with immune cells and modulate host cellular immune responses through exosomes. Growing evidence indicates that T. gondii-derived exosomes mediate communication between pathogens and immune cells, modulate host immune responses, and have great potential as new tools for tumor therapy. In this review, we highlight recent advances in isolation and identification techniques, profiling analysis, host immunomodulatory mechanisms, and the role of T. gondii-derived exosomes in tumor immunotherapy. Additionally, we emphasize the potential of T. gondii-derived exosomes as delivery platform to enhance anti-tumor efficacy in combination with other therapies. This review proposes that T. gondii-derived exosomes may serve as a novel tool for tumor immunotherapy owing to their ability to activate host immune function and properties such as high modifiability, stability, and low toxicity. This work will assist in promoting the application of parasite exosomes in tumor therapy. Keywords: Toxoplasma gondii, exosomes, tumor, immune regulation, immunotherapy

Yuling Liang,1,* Yuqing Xie,1,* Zhibo Dang,2,* Mengge Li,3,* Lihua Yu,1 Xinhui Wang,4 Peng Wang,5 Zhiyun Yang1 1Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Ethics Committee Office, Henan Province Hospital of TCM, Henan, People’s Republic of China; 3Department of Hepatobiliary Spleen and Stomach, Henan Province Hospital of TCM, Henan, People’s Republic of China; 4Beijing Children’s Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng Wang, Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Tel +86-10-84322530, Email dtpengwang@163.com; dtwangpeng@mail.ccmu.edu.cn Zhiyun Yang, Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Tel +86-10-84,322,148, Email yangzhiyun2016@163.comPurpose: Yiqi Liangxue Jiedu prescription (YLJP), a Chinese medicine that is commonly used to prevent liver cancer and is authorized by a national patent (patent No. ZL202110889980.5) has a therapeutic effect on precancerous lesions; however, the underlying mechanism remains unclear. This study is aimed at determining the clinical therapeutic efficacy of YLJP in patients with precancerous liver lesions and to explore and validate its possible effector mechanism.Patients and Methods: The 1-year incidence of hepatocellular carcinoma (HCC) was retrospectively analyzed in 241 patients with cirrhosis complicated by abnormal alpha-fetoprotein precancer. Network pharmacological analysis, molecular docking, and molecular dynamics simulation were used to explore the key targets and compounds of YLJP in treating HCC. Immunohistochemical methods were used to detect the expression of key proteins in tumor and cirrhotic tissues. Finally, the mechanism underlying the effects of YLJP was verified in rats with precancerous lesions.Results: The 1-year incidence of HCC was lower in the YLJP group than in the Western medicine group. The Wnt pathway protein, CTNNB1, is a key target of YLJP in preventing and treating HCC, and the canonical Wnt pathway is the key signaling pathway and is overexpressed in human liver tumors. In vivo experiments showed that YLJP significantly inhibited the canonical Wnt pathway and reduced the abnormal differentiation of hepatic oval cells. The binding of CTNNB1 to oleanolic acid, stigmasterol, and beta-sitosterol was found to be stable, indicating the action of these compounds in treating HCC.Conclusion: YLJP reduces the 1-year incidence of HCC, with its mechanism likely due to oleanolic acid, beta-sitosterol, and stigmasterol inhibition of the CTNNB1 activation of the β-catenin protein, which in turn regulates the Wnt signaling pathway and prevents the abnormal differentiation of hepatic oval cells into cancer cells, thus delaying the occurrence and progression of the disease.Keywords: network pharmacological analysis, molecular docking, molecular dynamics simulation, hepatocellular carcinoma, Wnt / β-catenin

Jie Liu, Yu Wei, Yanhui Zhu, Yu Li, Qiong Wang, Lei Yu, Langen Zhuang, Guoxi Jin, Xiaoyan Pei Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui Province, People’s Republic of ChinaCorrespondence: Guoxi Jin; Xiaoyan Pei, Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical University, No. 287 Changhuai Road, Bengbu, Anhui Province, 233000, People’s Republic of China, Email jyzjyz1999@163.com; 245899985@qq.comBackground: Thyroid hormone resistance syndrome (RTH) is a rare hereditary endocrine disease that can manifest as hyperthyroidism, hypothyroidism, or remain asymptomatic. It can easily be confused with other types of thyroid diseases. The diagnosis of the disease depends on genetic testing.Case Report: We report a 19-year-old male patient with elevation of thyroid hormones. Serological examination showed elevated thyroid hormone levels, and thyroid-stimulating hormone levels within the reference interval. The patient was finally diagnosed with RTH after genetic testing that identified a gene mutation inherited from his mother. Due to timely diagnosis, the patient’s condition has been well controlled, and his prognosis is good.Conclusion: The clinical manifestations of RTH lack specificity, and serological examination typically shows elevated thyroid hormone levels and unsuppressed thyrotropin levels. Differential diagnosis requires a combination of serological examination, imaging studies, and functional tests to distinguish RTH from other conditions. The purpose of this treatment is to improve symptoms and should not involve the blind administration of antithyroid drugs, thyroid surgery, or radiotherapy.Keywords: Inappropriate secretion of thyroid-stimulating hormone, resistance to thyroid hormone, thyroid hormone receptor β, THRB gene

Yu-Juan Zheng,1 Yong-Chao Hou,2 Hua Zhao,3 Xiao-Yun Wang,4 Yu-Dan Liu,3 Li Li,5 Liang Yu,6 Ming-Mei Guo1 1Department of Cardiology, Shanxi Provincial People’s Hospital, Taiyuan, 030012, People’s Republic of China; 2Department of Emergency, Shanxi Provincial People’s Hospital, Taiyuan, 030012, People’s Republic of China; 3College of Nursing, Shanxi University of Chinese Medicine, Jinzhong, 030619, People’s Republic of China; 4Department of Endocrinology, Shanxi Provincial People’s Hospital, Taiyuan, 030012, People’s Republic of China; 5Department of Gynecology, Shanxi Provincial People’s Hospital, Taiyuan, 030012, People’s Republic of China; 6Neonatal Disease Screening Center, Shanxi Provincial Children’s Hospital, Taiyuan, 030013, People’s Republic of ChinaCorrespondence: Ming-Mei Guo, Department of Cardiology, Shanxi Provincial People’s Hospital, No. 29 Shuangtasi Street, Yingze District, Taiyuan, 030012, People’s Republic of China, Tel +86 13934533989, Email guomingmeigmm@126.comObjective: To conduct an in-depth exploration of the factors influencing unfulfilled needs in caregivers of patients with phenylketonuria.Methods: A rapid qualitative analysis approach was used to conduct semi-structured interviews with 16 caregivers of patients with phenylketonuria undergoing specialized dietary interventions, along with 5 medical professionals, within a designated phenylketonuria diagnosis and treatment center in Shanxi Province. Interview data were systematically organized, analyzed, and thematically extracted.Results: Four primary themes were extracted: self-imposed constraints (including insufficient caregiver engagement, economic limitations, and stigma); interpersonal constraints (encompassing social isolation, inadequate social support networks, and lack of doctor-patient interactions); structural limitation factors (inadequate provision of specialized professional support systems, lack of medical dietary supplements, and deficiencies in national policies); and experiential limitation factors (encompassing sensory perceptions of medical dietary supplements and insufficient continuity in psycho-emotional care).Conclusion: The unfulfilled needs of caregivers of patients with phenylketonuria primarily manifest across four dimensions. Greater emphasis on addressing these needs is warranted, necessitating increased attention to patients with phenylketonuria and their caregivers. Specifically, the focus should be directed toward addressing their emotional requirements, along with proactive development of the medical service infrastructure. Such measures are imperative for reducing unfulfilled needs among caregivers of patients and enhancing their prognosis.Keywords: caregivers, influencing factors, phenylketonuria, qualitative research, rare diseases, unmet needs

Lihua Yu,1,2,* Chunxia Zhang,3,* Jie Yang,4 Lu Li3 1Department of Pediatric Dentistry, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, 300041, People’s Republic of China; 2Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, People’s Republic of China; 3Tianjin Baogang Rare Earth Research Institute Co., Ltd, Tianjin, 300300, People’s Republic of China; 4Department of Stomatology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunxia Zhang, Tianjin Baogang Rare Earth Research Institute Co., Ltd, Block B, Building 5, No. 6, Huafeng Street, Huaming High-Tech Industrial Zone, Dongli District, Tianjin, 300300, People’s Republic of China, Tel +86-022-58910562, Email zcx19941002@163.comPurpose: The primary goals of endodontic therapy are to eliminate microbes and prevent reinfection. Persistent root canal infections and failure of root canal therapy are primarily attributed to the presence of bacteria, particularly E. faecalis. Chemical irrigants play a crucial role in complementing mechanical instrumentation in ensuring adequate disinfection. However, current techniques and available irrigants are limited in their ability to achieve optimal sterilization of the root canal system. In this study, we developed a novel material called La@PCDs by combining CQD-PVA and lanthanum for root canal irrigation.Methods: A one-pot hydrothermal method was used to prepare composites of lanthanum and CQD-PVA (La@PCDs). Scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy and the particle size were employed to characterize La@PCDs. ROS generation was evaluated by measuring the fluorescence intensity emitted at 525 nm from 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA). In vitro experiments were conducted to assess the effectiveness of the nanoparticles in combating Enterococcus faecalis and eradicating in situ biofilm eradication in root canal. Furthermore, cytotoxicity assessments were carried out to demonstrate the safety of La@PCDs.Results: SEM and FTIR results showed that La@PCDs were successfully prepared and exhibiting a homogeneous size distribution and irregular morphology. ROS assessment demonstrated that La@PCDs have a synergistic effect, promoting the production of a large number of ROS. This effect only occurred under acidic PH conditions. The inherent acidity in the biofilm microenvironment can act as internal stimulus. In vitro experiments revealed superior antibacterial efficiency under acidic conditions without causing significant cytotoxicity compared to the commonly used NaClO irrigant. The biosafety of La@PCDs was confirmed.Conclusion: Compared to existing materials, these nanoparticles exhibit favorable antibacterial and anti-biofilm properties, along with improved biocompatibility. These findings emphasize the potential of the integrated La@PCDs as a promising option for enhancing root canal irrigation and disinfection.Keywords: lanthanum, La, reactive oxygen species, ROS, pH-response, antimicrobial, root canal irrigation

Мета. Дослідити сучасний стан і структуру національних сортових рослинних ресурсів, проаналізувати динаміку їхнього формування, встановити нові виклики та загрози, що постають перед національними інтересами й продовольчою безпекою держави. Методи. У процесі досліджень використовували загальнонаукові методи, зокрема гіпотези, спостереження, пошуковий з елементами екстраполяції джерелознавчої бази даних; аналізу, порівняльного оцінювання та синтезу для формування висновків. Результати. Фізико­географічне розташування України в центрі Європи визначає ресурсний експортно­імпортний сегмент сортів та гібридів, який залежить від міжнародних тенденцій і трендів продовольчого ринку. Останнім часом наша держава втрачає передові позиції на ринку сортових ресурсів сільськогосподарських культур. Частка сортів українських заявників у Державному реєстрі сортів рослин, придатних для поширення в Україні, на початку третього кварталу 2024 року була меншою, ніж іноземних, і трохи перевищувала 44% (кукурудзи – 45,3%, соняшнику – 32,9%, овочів – 23,3%, ріпаку – 19,1%, буряків – 19,2%). Наразі збережено пріоритетність вітчизняної селекції для таких груп: зернові – 52,3%, кормові – 64,2%, лікарські – 88,7%. За прогнозами фахівців, найближчими роками три четверті вирощуваних у нашій державі сортів сільськогосподарських культур будуть мати іноземне походження. Ця ситуація спричиняє значне занепокоєння не лише через посилення імпортної залежності, але й реальну перспективу занепаду вітчизняної селекції та формування ризиків у сфері охорони прав на сорти рослин. Проаналізовано причини такого стану національних сортових ресурсів і тенденції розвитку галузі насінництва основних стратегічних видів з огляду на виробництво насіння як іноземної, так і вітчизняної селекції, частку якого на ринку встановлено під час досліджень. Визначено обсяги та основних виробників кондиційного насіння в Україні. Висновки. Проаналізовано стан сортових рослинних ресурсів, виявлено тенденції та основні проблеми, що виникають у процесі їхнього формування. Визначено головні напрями розвитку та імплементації до норм європейського вітчизняного законодавства у сфері охорони прав на сорти рослин і насінництва.

Yihong Tai,1,* Haonan Wang,1,* Yinghong Dai,2,* Liang Yu1,3 1Department of Exercise Physiology, School of Sport Science, Beijing Sport University, Beijing, 100084, People’s Republic of China; 2Xiangya School of Medicine, Central South University, Changsha, 410008, People’s Republic of China; 3Engineering Research Center of Strength and Conditioning Training Key Core Technology Integrated System and Equipment of Ministry of Education, Beijing Sport University, Beijing, 100084, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang Yu, Engineering Research Center of Strength and Conditioning Training Key Core Technology Integrated System and Equipment of Ministry of Education, Beijing Sport University, Beijing, 100084, People’s Republic of China, Tel/Fax +86 1062967640, Email yuliang@bsu.edu.cnBackground: Sleep disorders and low grip strength often co-occur clinically and are geriatric symptoms that cause significant socioeconomic burden. Previous observational studies have found an association between sleep behaviors and grip strength, but the causal relationship remains unclear.Purpose: With the Mendelian randomization (MR) approach, the study aimed to determine the causal association between sleep traits (sleep duration, insomnia, daytime napping, sleep-wake disorders, chronotype) and low grip strength.Methods: The study used genetic variants from the genome-wide association study (GWAS) archived in UK Biobank and FinnGen. We assessed the potential causal relationship between sleep behaviors and grip strength using inverse variance weighting (IVW), weighted median (WM), and MR-Egger. Additionally, we performed sensitivity analyses using Cochran’s Q test, MR Egger Intercept test, funnel plots, and leave-one-out method.Results: We found that sleep duration is causally negatively associated with low grip strength (OR = 0.618, 95% CI = 0.424– 0.900, P = 0.012). Sleep-wake disorders have a positive association with low grip strength (OR = 1.018, 95% CI = 1.002– 1.034, P = 0.029). Reversely, high low grip strength risk was causally associated with increased daytime napping (OR = 1.018, 95% CI = 1.004– 1.032, P = 0.011).Conclusion: The study revealed causal associations between sleep duration, sleep-wake disorders, and low grip strength. Understanding their relationship helps in early clinical intervention to improve the life quality of the elderly.Keywords: sleep, low grip strength, Mendelian randomization

Lanqi Yu,1,2 Xiaolu Wu,1,2 Qinhan Zhang,1,2 Binghai Sun1,2 1School of Psychology, Zhejiang Normal University, Jinhua, Zhejiang, People’s Republic of China; 2Intelligent Laboratory of Child and Adolescent Mental Health and Crisis Intervention of Zhejiang Province, Zhejiang Normal University, Jinhua, Zhejiang, People’s Republic of ChinaCorrespondence: Qinhan Zhang; Binghai Sun, School of Psychology, Zhejiang Normal University, 688 YingBin Road, Jinhua, Zhejiang, People’s Republic of China, Email Qinhanzhang@zjnu.edu.cn; jky18@zjnu.cnPurpose: Within the scope of secondary education, social adjustment among students signifies their ability to effectively engage in social activities and adapt to shifting social environments. Extensive research across diverse geographical and sociocultural landscapes has demonstrated a positive correlation between social support and social adjustment; nonetheless, the specific mechanisms that facilitate this correlation among secondary school students remain largely unexplored. This study examines the roles of subjective well-being and psychological resilience as potential mediators in the connection between social support and social adjustment.Participants and Methods: To achieve this, a descriptive correlation design was employed with four measures, including Social Support Scale, Social Adjustment Diagnosis Scale, Adolescent Students’ Life Satisfaction Scale, and the Chinese version of Mental Toughness Inventory (MTI). A total of 1537 valid responses from secondary school students across Zhejiang province (China) were collected, of which 786 were boys (51.1%) and 751 girls (48.9%), with average age of 16.89 years (SD = 0.79).Results: This research demonstrates that social support, along with subjective well-being and psychological resilience, significantly and positively influences social adjustment. It was observed that both subjective well-being and psychological resilience, whether occurring simultaneously or in succession, partially mediate the influence of social support on social adjustment.Conclusion: The implications of this research suggest that enhancing social adjustment among secondary school students can be achieved by increasing their levels of social support, thereby boosting subjective wellbeing and fortifying psychological resilience. Within the environment of secondary schools, augmenting social support leads to improved social adjustment; furthermore, enhancing subjective wellbeing and reinforcing psychological resilience are crucial for supporting students’ positive adaptation to dynamic social environments. Teachers and educational policymakers could implement training programmes, provide psychological counselling, and bolster home-school collaboration as strategies to foster better social adjustment among students. Keywords: social support, social adjustment, subjective well-being, psychological resilience, Chinese

Mucormycosis is a severe mycotic infection with high mortality among immunocompromised patients. Its in- cidence in solid organ transplant recipients is 2–8% of all invasive fungal infections. In most cases, it occurs in the late posttransplant period. Risk factors in this patient cohort are graft-versus-host disease (GvHD) and use of immunosuppressive drugs. The article describes clinical cases of mucormycosis and analysis of literature data on the problem of invasive mucormycosis in solid organ transplant recipients. It also reviews the main methods of diagnosis and treatment of the disease according to international guidelines.

The cardiovascular system during pregnancy undergoes a number of compensatory and adaptive changes, such as an increase in heart rate, cardiac output and total peripheral resistance, which causes an increase in the load on the myocardium. Peripartum cardiomyopathy is a serious polyetiological complication of pregnancy and the postpartum period, as well as an important cause of disability and mortality for both mother and fetus. The non-specificity of complaints and the paucity of clinical symptoms in the early stages of the disease lead to delayed diagnosis and significantly increase the frequency of unfavorable outcomes. In the article we present our own clinical observation of the acute development of severe peripartum cardiomyopathy in a multipregnant woman at 36 weeks of gestation, complicated by cardiogenic shock and antenatal fetal death.

Zuo Wang,1,2,&ast; Siqi Guo,3,&ast; Chong He,2,4,&ast; Lingling Chen,5 Jinxia Wang,2 Wenbo Xiu,2 Gao Zhang,2 Yang Chen,2 An Li,2 Xiong Zhu,6 Xiao Xiao,2 Ling Yu,3 Fang Lu2,4,7 1Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Department of Ophthalmology, Daping Hospital, Army Medical Center, Army Medical University, Chongqing, People’s Republic of China; 4Medico-Engineering Cooperation on Applied Medicine Research Center, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 5Department of Immunology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, People’s Republic of China; 6Department of Prenatal Diagnosis, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 7Health Management Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Yu; Fang Lu, Email oculistlingyu@hotmail.com; lufangfang@126.comObjective: Evidence suggests that dysbiosis of the gut microbiota plays a pivotal role in the development of glaucoma. This dysbiosis is commonly associated with chronic intestinal inflammation and increased intestinal permeability. However, the understanding of intestinal inflammation and permeability in glaucoma remains insufficient. This study aims to investigate the potential relationship between fecal inflammation and permeability markers and glaucoma.Methods: We recruited 114 glaucoma patients and 75 healthy controls. Levels of fecal lactoferrin (Lf) and alpha-1 antitrypsin (AAT) were quantified using enzyme linked immunosorbent assay (ELISA) to compare both biomarkers between groups and across different severity grades of glaucoma. Logistic regression analysis was used to assess the association between these fecal biomarkers and glaucoma. The severity of glaucoma was assessed based on the mean deviation (MD) in the visual field.Results: In this study, we observed elevated levels of fecal Lf and AAT in glaucoma patients. The proportion of glaucoma patients with abnormal fecal Lf levels (≥ 7.25 μg/g) was significantly higher than that of the controls (p = 0.012). A positive correlation was noted between fecal Lf and AAT (rho = 0.20, p = 0.006). After adjusting for age and sex, multivariable logistic regression analysis indicated that both fecal Lf (OR = 1.11, 95% CI: 1.01– 1.21, p = 0.026) and AAT (OR = 1.01, 95% CI: 1.01– 1.02, p < 0.001) positively correlated with glaucoma. These biomarkers might reflect glaucoma severity, with significant differences in fecal Lf levels observed between moderate and severe stages, but not in the early stage. Furthermore, increasing levels of fecal AAT correlated with greater severity of glaucomatous injury and a larger vertical cup-to-disc ratio (VCDR) (p < 0.05).Conclusion: This study suggests an increase in intestinal inflammation and permeability in glaucoma, further indicating the importance of the ‘gut-retina axis’ in the pathogenesis of the disease and potentially offering new therapeutic avenues.Keywords: fecal lactoferrin, fecal alpha-1 antitrypsin, glaucoma, intestinal inflammation, intestinal permeability, intestinal barrier

Objective: to investigate the clinical and instrumental manifestations of axial psoriatic arthritis (axPsA) in combination with hyperuricemia (HU). Material and methods. The study included 71 patients with psoriatic arthritis (PsA): 59 (83%) men and 12 (17%) women. These patients had clinical and imaging evidence of inflammatory changes in the spine and were diagnosed with axPsA. The mean age of patients was 45.7±11.3 years, duration of psoriasis (Ps) was 209.3±163.4 months, and duration of PsA was 51.9±45.5 months. Patients underwent standard clinical, laboratory and radiological examinations. Patients completed the PsAID-12, FACIT-F and FiRST questionnaires and their LEI, MASES, DAPSA, BASDAI, BASFI, BASMI, ASDAS-CRP and BSA indices were assessed. Data on concomitant diseases and drug therapy were also collected. HU was diagnosed at uric acid (UA) level of >360 μmol/L. Patients were divided into two groups – with HU (group 1, n=24, 33.8%) and without HU (group 2, n=47, 66.2%). Results and discussion. The mean UA level was 329.96±80.2 μmol/l. The age of the patients, the duration of Ps and PsA were comparable in both groups. The activity of PsA and spondylitis in the two groups also did not differ. No significant differences were found between the groups in frequency of sacroiliitis or presence of erosions. In the 1st group, the total number of syndesmophytes in two sections of the spine was significantly higher (n=26, 108%) than in the 2nd group (n=39, 83%), p=0.04. In the group of patients with HU, there was a higher intensity of nocturnal spinal pain compared to the group without HU (5.0±2.7 and 3.6±2.8, respectively; p=0.04), more pronounced sleep disturbances (11±5.2 and 7±5.9; p=0.04), higher triglyceride levels (median 0.92 [0; 1.66] and 0.3 [0; 0.6]; p=0.03) and a higher frequency of hypertriglyceridemia (n=2, 8.3% and n=0; p=0.04) and liver steatosis (n=7, 29.1% and n=5, 10.6%; p=0.04, respectively). Patients with HU received antihypertensive therapy (n=10, 41.7% and n=14, 29.8% respectively; p=0.04) and urate-lowering medications (n=4, 16.6% and n=1, 2.1% respectively; p=0.02) significantly more often than patients without HU. Conclusion. HU was present in one third of patients with axPsA. They were more likely to have multiple syndesmophytes in the spine, metabolic disturbances, more severe nocturnal spinal pain and more pronounced sleep disturbances.

Objectives. Cationic amphiphiles and antimicrobial peptidomimetics are widely investigated as antibacterial agents due to their membrane-active mechanism of action. Particular attention is focused on the rational design of compounds in this class to achieve high antimicrobial activity. The aim of the present work is to synthesize bivalent cationic amphiphiles with L-ornithine as a branching element and evaluate the effectiveness of their antibacterial action. The compounds differ in terms of hydrophobicity due to the variation of N-terminal aliphatic amino acids in the polar block and alternation of dialkyl and alkyl-hetaryl radicals in the lipophilic block.Methods. For the synthesis of nonpolar fragments of amphiphiles, methods for the alkylation of amines with alkyl bromides in the presence of carbonate salts were used. The formation of amide bonds of L-ornithine derivatives with amino acids was carried out using the carbodiimide method. For the reaction products recovery from the reaction mixture, column chromatography on silica gel and aluminum oxide activated Brockmann Grade II was used. The antimicrobial activity of the synthesized compounds against gram-positive B. subtilis 534 and gram-negative E. coli M17 bacterial strains was evaluated. Minimum inhibitory concentration (MIC) values were recorded using a serial microdilution method in a nutrient medium.Results. Developed schemes for the preparation of bivalent cationic amphiphiles based on L-ornithine derivatives are presented. Differences in the structure of aliphatic amino acids (glycine, β-alanine, γ-aminobutyric acid (GABA)), in the length of alkyl radicals (C8, C12), or in the presence of an indole moiety, were used in the design of target compounds. The high antibacterial activity of the synthesized compounds was demonstrated. The most active compounds were lipoamino acids with terminal GABA residues and asymmetrical non-polar block (tryptamyl–dodecylamine). The MIC values were 0.39 μg/mL for gram-positive bacteria and 1.56 μg/mL for gram-negative bacteria. A GABA derivative with a symmetrical lipophilic moiety based on dioctylamine demonstrated activity with an MIC of 0.78 μg/mL against B. subtilis and 3.12 μg/mL against E. coli.Conclusions. Nine new lipoamino acid cationic bivalent amphiphiles based on L-ornithine were synthesized. The structure of the obtained compounds was confirmed by nuclear magnetic resonance 1H spectroscopy and mass spectrometry data. Leading compounds in antimicrobial activity against both gram-positive and gram-negative strains of bacteria were determined. The influence of the degree of lipophilicity in the asymmetric nonpolar block on the level of exhibited antimicrobial activity is demonstrated.

Yun Han,1,&ast; Jianping Zhu,1,&ast; Jieqiong Liu,2 Ying Zheng,2 Gang Liang,1 Yi Yang,1 Lingyan Yu,3 Zhenwei Yu,1 Gang Han1 1Research Center for Clinical Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China; 2The 903rd Hospital of PLA Joint Logistic Support Force, Hangzhou, People’s Republic of China; 3Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenwei Yu; Gang Han, Email yzw_srrsh@zju.edu.cn; 3199022@zju.edu.cnIntroduction: Recent studies suggested the potential benefits of extended infusion times to optimize the treatment efficacy of ceftazidime/avibactam, which indicated that the current pharmacokinetic/pharmacodynamic (PK/PD) target may not be sufficient, especially for severe infections. The purpose of this study is to assess the adequacy of dosing strategies and infusion durations of ceftazidime/avibactam when applying higher PK/PD targets.Methods: This study utilized published PK parameters to conduct Monte Carlo simulations. Different dosages including the recommended regimen based on renal function were simulated and evaluated by the probability of target attainment (PTA) and cumulative fraction of response (CFR). Different PK/PD targets were set for ceftazidime and avibactam. MIC distributions from various sources were used to calculate the CFR.Results: Multiple PK/PD targets have been set in this study, All recommended dosage could easily achieve the target of 50%fT ≥ MIC (ceftazidime) and 50%fT ≥ CT=1.0 mg/L (avibactam). However, for severe infection patients with normal renal function and augmented renal clearance at the recommended dosage (2000 mg/500 mg, every 8 hours), the infusion duration needs to be extended to 3 hours and 4 hours to achieve the targets of 100%fT ≥ MIC and 100%fT ≥ CT=1.0 mg/L. Only continuous infusion at higher dosages achieved 100%fT ≥ 4×MIC and 100%fT ≥ CT=4.0 mg/L targets to all currently recommended regimens. According to the varying MIC distributions, higher concentrations are needed for Pseudomonas aeruginosa, with the attainment rates vary across different regions.Conclusion: The current recommended dosing regimen of ceftazidime/avibactam is insufficient for severe infection patients, and continuous infusion is suggested.Keywords: ceftazidime, avibactam, pharmacokinetic/pharmacodynamic, probability of target attainment

Introduction. There is evidence of a connection between infectious and inflammatory lesions of the lower urinary tract and bladder cancer (BCa). However, there is virtually no data on the urine microbiota of middle-aged and elderly men with suspected BCa. This knowledge is extremely important from the point of view of studying the role of the infectious-inflammatory hypothesis in the genesis of BCa.Objective. To conduct a comparative assessment of the microbiota of bladder urine obtained during natural urination and bladder catheterization through standard and extended cultural studies in men with a presumptive diagnosis of non-muscle-invasive bladder cancer (NMIBC).Materials & methods. The prospective comparative study with consecutive patient recruitment included 23 men older than 45 years with suspected NMIBC based on clinical, laboratory and sonographic data, as well as with no history of infectious and inflammatory diseases of the kidneys and urinary tract, including sexually transmitted infections and recurrent infections of other organs and systems. A midstream urine samples and catheter-drained urine immediately before urethrocystoscopy were subjected to bacteriological analysis. Urine culture study was carried out using a standard set of nutrient media under aerobic cultivation conditions and an expanded set of nutrient media under aerobic and anaerobic cultivation conditions.Results. An anaerobic spectrum of microorganisms was predominantly detected in the urine of patients with suspected NMIBC. Moreover, Peptococcus spp. was more often found among anaerobic taxa. (70%), Eubacterium spp., Propionibacterium spp. (45% each, respectively), among representatives of the aerobes — Corynebacterium spp. (60%), S. lentus (up to 45%), S. haemolyticus (35%) and E. faecalis (30%). Data from a comparative analysis of the detection frequencies of microorganisms depending on the method of collecting material and the set of media for cultivation showed that more isolates are isolated in the midstream urine samples than in the study of catheter urine (2.9- and 1.9-fold with the standard and extended sets of media, respectively). In addition, when performing an extended bacteriological study compared to the standard method, the detection of microorganisms is 3.5-fold higher when examining an average portion of urine and 5.1-fold higher when examining catheter urine. The average number of microorganisms per one patient is also higher when using the extended method (midstream portion — 4.7 ± 1.9; catheterised urine — 2.3 ± 1.0) in comparison with the standard one (midstream portion — 1.3 ± 0.9; catheterised urine — 0.3 ± 0.5).Conclusion. Middle-aged and older men with NMIBC are characterized by asymptomatic bacteriuria in the form of a wide range of aerobic and anaerobic microorganisms. The urine pattern obtained with a urethral catheter contains a significantly narrower range of bacteria compared to the sample obtained through natural urination. It is advisable to carry out an extended cultural urine examination to study the characteristics of the microbiota / microbiome of the urine of the bladder immediately before the urethrocystoscopy procedure by collecting urine with a urethral catheter.