In recent years， repetitive transcranial magnetic stimulation （rTMS） has garnered significant attention as a therapeutic approach for sleep disorders in the elderly. However， the prevailing rTMS protocols are predominantly developed based on normative neurophysiological data derived from young adults and fail to incorporate individualized parameters tailored to the brain characteristics of the elderly. To address this gap， the consensus development group synthesized the latest evidence from 2010 to 2025 and established a standardized rTMS protocol specifically for elderly patients with sleep disorders. Adhering to the Appraisal of Guidelines for Research and Evaluation II （AGREE II） framework， systematically screened randomized controlled trials （RCTs） and systematic reviews regarding rTMS in the treatment of sleep disorders across various conditions. Meanwhile， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system was employed to rigorously grade the quality of evidence and the strength of recommendations. This consensus guideline delineates precise rTMS protocols for the management of sleep disorders in the elderly， highlights the adjustment of stimulation intensity according to scalp-cortex distance recommends either MRI‑guided neuronavigation or the Beam F3/F4 heuristic approach for accurate target localization， thereby providing precise rTMS intervention protocol for sleep disorders in the elderly， aiming to enhance clinical efficacy while ensuring treatment safety. ［Funded by National Key Research and Development Program （number， 2023YFC3603200）； General Program of Shenzhen Science and Technology Innovation Commission （number， JCYJ20240813112859008， JCYJ20240813112900002）； Youth Program of Shenzhen Kangning Hospital （number， KN2023A004）； www.guidelines-registry.cn number， PREPARE-2026CN530］

Objective To construct a library of human-derived anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) single-chain variable fragments (scFv) and screen for broad-spectrum neutralizing antibodies to identify candidate molecules for the development of diagnostic and therapeutic agents. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from the peripheral blood of patients who had recovered from novel coronavirus infection. Total RNA was extracted from these PBMCs and reverse transcribed into cDNA, which was used as a template for constructing a human anti-SARS-CoV-2 scFv library. Phage display technology was used to screen for scFv antibodies specific to the SARS-CoV-2 S protein. Full-length IgG antibodies were synthesized through sequence analysis and human IgG expression, and their binding capacity and neutralizing activity against SARS-CoV-2 were evaluated. Results A human-derived scFv antibody library against SARS-CoV-2 with a capacity of 1.56×10⁷ CFU was successfully constructed. Two specific scFv antibodies were screened from this library and expressed as full-length IgG antibodies (IgG-A10 and IgG-G6). IgG-A10 exhibited strong neutralizing activity against both the original SARS-CoV-2 strain (WT) and the XBB subvariant of the Omicron variant. However, the neutralizing activity of this antibody against the JN.1 sub lineage of the Omicron BA.2.86 variant was moderate. Conclusion This study has successfully constructed a human anti-SARS-CoV-2 scFv antibody library from the peripheral blood of recovered patients, and screened and expressed anti-SARS-CoV-2 IgG antibodies with neutralizing activity, laying a foundation for the prevention, diagnosis, and treatment of SARS-CoV-2 infection.
Humans ; Single-Chain Antibodies/genetics* ; SARS-CoV-2/immunology* ; COVID-19/immunology* ; Immunoglobulin G/genetics* ; Antibodies, Viral/genetics* ; Peptide Library ; Spike Glycoprotein, Coronavirus/immunology* ; Antibodies, Neutralizing/immunology* ; Leukocytes, Mononuclear/immunology* ; Broadly Neutralizing Antibodies/immunology*

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Humans ; Transcranial Magnetic Stimulation ; Pain Management ; Psychotic Disorders/therapy* ; Depressive Disorder, Major ; Treatment Outcome ; Transcranial Direct Current Stimulation

Humans ; Perinatology ; Delivery of Health Care

With the growing influence of slow population growth and population aging, China has established the birth policy and issued a series of documents to promote maternal and fetal health and improve the birth rate. With the increase in prevalence of birth defects, timely diagnosis and intervention in utero provide possibilities to reduce unnecessary abortions and offer better prognosis. Congenital heart disease (CHD), as one of the most common congenital birth defects, is the leading cause of mortality in patients aged <5 years, and brings a heavy burden to both the affected families and society. Fetuses with CHD are associated with an increased risk of pregnancy-related complications and premature birth, and children with CHD typically face growth and developmental problems even after the correction of malformation. Therefore, management including diagnosis, treatment, and rehabilitation throughout the fetal period into childhood and even adulthood is essential for children with CHD. Based on the rapid advances in intrauterine and perinatal medicine and an in-depth collaboration among obstetrics and pediatrics, a novel diagnosis and treatment system has been established for the management of CHD in the past 2 decades in Shanghai Xinhua Hospital. This Intrauterine Diagnosis and Treatment System and Comprehensive Lifecycle Health Service of Congenital Heart Disease model provides prenatal diagnosis, intrauterine intervention, delivery room service and neonatal therapies, and postintrauterine rehabilitation for children with CHD. We have developed a four-dimensional spatiotemporal image correlation echocardiography and a three-dimensional cardiac virtual endoscopy system for the intrauterine diagnosis of CHD, dramatically raising the diagnostic utility. Our innovative and independent newborn-intervention technique has effectively reduced the re-intervention rate in patients with pulmonary atresia with intact ventricular septum and critical pulmonary stenosis. In 2018, Xinhua Hospital independently performed the case of fetal aortic valvuloplasty in Asia through a multidepartment collaborative effort. All children treated in this system achieved biventricular circulation and a better long-term postoperative outcome. We also have conducted postoperative rehabilitation therapy to promote the development and health of children with CHD. The practice of Xinhua model has reduced unnecessary abortion of CHD fetuses, reduced the mortality rate associated with critical CHD, and improved the mid- and long-term prognosis in CHD, which is essential to promote the fertility level and children’s health. Furthermore, translational medicine platform and the birth cohort Early Life Plan was constructed to explore the origins of major developmental diseases and establish an early intervention model in CHD. This practice of assessment of the intrauterine system has been expanded to other congenital defects in Xinhua Hospital, and sequential treatment of more than 2,000 cases has been completed to date. Based on practice in intrauterine management of CHD and other diseases, the concept of Intrauterine Pediatrics was proposed as a first to emphasize early prevention and intervention of childhood diseases and promote a comprehensive lifecycle service for children. The development and evolution of this system requires further attention not only from researchers but also from the government and global medical communities.

With the growing influence of slow population growth and population aging, China has established the birth policy and issued a series of documents to promote maternal and fetal health and improve the birth rate. With the increase in prevalence of birth defects, timely diagnosis and intervention in utero provide possibilities to reduce unnecessary abortions and offer better prognosis. Congenital heart disease (CHD), as one of the most common congenital birth defects, is the leading cause of mortality in patients aged <5 years, and brings a heavy burden to both the affected families and society. Fetuses with CHD are associated with an increased risk of pregnancy-related complications and premature birth, and children with CHD typically face growth and developmental problems even after the correction of malformation. Therefore, management including diagnosis, treatment, and rehabilitation throughout the fetal period into childhood and even adulthood is essential for children with CHD. Based on the rapid advances in intrauterine and perinatal medicine and an in-depth collaboration among obstetrics and pediatrics, a novel diagnosis and treatment system has been established for the management of CHD in the past 2 decades in Shanghai Xinhua Hospital. This Intrauterine Diagnosis and Treatment System and Comprehensive Lifecycle Health Service of Congenital Heart Disease model provides prenatal diagnosis, intrauterine intervention, delivery room service and neonatal therapies, and postintrauterine rehabilitation for children with CHD. We have developed a four-dimensional spatiotemporal image correlation echocardiography and a three-dimensional cardiac virtual endoscopy system for the intrauterine diagnosis of CHD, dramatically raising the diagnostic utility. Our innovative and independent newborn-intervention technique has effectively reduced the re-intervention rate in patients with pulmonary atresia with intact ventricular septum and critical pulmonary stenosis. In 2018, Xinhua Hospital independently performed the case of fetal aortic valvuloplasty in Asia through a multidepartment collaborative effort. All children treated in this system achieved biventricular circulation and a better long-term postoperative outcome. We also have conducted postoperative rehabilitation therapy to promote the development and health of children with CHD. The practice of Xinhua model has reduced unnecessary abortion of CHD fetuses, reduced the mortality rate associated with critical CHD, and improved the mid- and long-term prognosis in CHD, which is essential to promote the fertility level and children’s health. Furthermore, translational medicine platform and the birth cohort Early Life Plan was constructed to explore the origins of major developmental diseases and establish an early intervention model in CHD. This practice of assessment of the intrauterine system has been expanded to other congenital defects in Xinhua Hospital, and sequential treatment of more than 2,000 cases has been completed to date. Based on practice in intrauterine management of CHD and other diseases, the concept of Intrauterine Pediatrics was proposed as a first to emphasize early prevention and intervention of childhood diseases and promote a comprehensive lifecycle service for children. The development and evolution of this system requires further attention not only from researchers but also from the government and global medical communities.

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. The metabolic changes of atrial myocytes, especially lipid metabolism, have a significant impact on the electrical signals and structural remodeling of atrial tissue, and play an important role in the occurrence and development of AF. The reduction of fatty acid oxidation ratio and increased aerobic glycolysis ratio are characteristic changes of tissue metabolic remodeling in AF. In this review, we will introduce the latest research status of lipid metabolism in AF from aspects of AF metabolism, clinical treatment and diagnosis and prognosis.

Objective:To compare the results of high-resolution colonic manometry (HRCM) in patients with four subtypes of constipation: slow transit constipation(STC), outlet obstruction constipation (OOC), mixed STC and OOC, and normal transit constipation(NTC), and to explore the intestinal motility characteristics of patients with different subtypes of constipation.Methods:From 20th January 2017 to 20th September 2020, the HRCM results of 225 patients with functional constipation who visited the Department of Anorectal Surgery of Tianjin Union Medical Center were retrospectively analyzed. According to the results of colonic transit test, 225 patients were divided into STC group (108 cases), OOC group (36 cases), mixed group (28 cases) and NTC group (53 cases). General information such as Wexner constipation scores, clinical symptoms (decreased desire to defecate, sensation of anorectal blockage, hand-assisted defecation, spontaneous bowel movements frequency<3 times per week), the incidence, frequency within one day (hereinafter referred to as frequency), average velocity, average wave amplitude, average duration of contraction, average length of contraction, and the dynamic index (DI) of average pressure of high-amplitude propagating contraction (HAPC), as well as the frequency, average wave amplitude, average duration of contraction, and the DI of average pressure of low-amplitude propagating contraction (LAPC) were compared among the four groups. One-way ANOVA and multiple comparison, Kruskal-Wallis test and chi-square test were used for statistical analysis.Results:The Wexner constipation scores of the STC, OOC, mixed and NTC group were 13.17±4.04, 13.97±4.55, 11.36±4.03 and 11.58±4.06, respectively, and the difference was statistically significant ( F=3.879, P<0.05). The Wexner consipation scores of the STC and OOC group were both higher than the mixed and NTC group, and the difference were statistically significant (One-way ANOVA and multiple comparison, all P<0.05). The proportion of decreased desire to defecate, sensation of anorectal blockage, hand-assisted defecation, spontaneous bowel movements frequency<3 times per week of STC, OOC, mixed and NTC group were 47.2% (51/108), 36.1% (13/36), 14.3% (4/28), 20.8% (11/53); 42.6% (46/108), 75.0% (27/36), 46.4% (13/28), 64.2% (34/ 53); 31.5% (34/108), 38.9% (14/36), 3.6% (1/28), 18.9% (10/53); 90.7% (98/108), 77.8% (28/36), 82.1% (23/28) and 62.3% (33/53), and the differences were statistically significant ( χ2=17.093, 12.463, 13.437 and 18.927; all P<0.01). The proportion of decreased desire to defecate of STC group was higher than that of mixed and NTC group, and spontaneous bowel movements frequency<3 times per week was higher than that of OOC and NTC group, and the differences were statistically significant ( χ2=10.014, 10.518, 4.418 and 19.016; all P<0.05). The proportion of sensation of anorectal blockage of OOC group was higher than that of STC and mixed group, and the proportion of hand-assisted defecation was higher than that of the mixed and NTC group, and the differences were statistically significant ( χ2= 9.511, 5.486, 10.948 and 4.363, all P<0.05). The incidence of HAPC in STC, OOC, mixed and NTC groups was 39.8% (43/108), 36.1% (13/36), 57.1% (16/28), and 60.4% (32/53), respectively, and the difference was statistically significant ( χ2=8.880, P=0.031). The incidence of HAPC in STC group and OOC group were lower than that of NTC group, and the differences were statistically significant ( χ2=6.041 and 5.050, P=0.014 and 0.025). There were no statistically significant difference in the frequency, average velocity, average amplitude, average duration of contraction, average length of contraction and DI of pressure of HAPC in four groups, and there were no statistically significant difference in the frequency, average amplitude, average duration of contraction, and DI of pressure of LAPC in the four groups (all P>0.05). Conclusions:Doctors can more clearly and objectively observe the intestinal motility characteristics of patients with different subtypes of constipation through HRCM. HRCM provides a strong basis for the diagnosis and further treatment of functional constipation, and has a high clinical application value.