A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Objective To study the bioequivalence of two glipizide tablets in healthy Chinese subjects.Methods Randomized,open,single-administration,two-period,self-cross-over trial design was used in the study.There were 28 Chinese healthy subjects in the fasted state and 28 in the fed state,complete repeat cross single dose oral glipizide tablets test preparation or reference preparation 5 mg.The plasma concentration of glipizide was determined by liquid chromatography/tandem mass spectrometry at different time points after administration.The non-compartmental model was used to calculate the pharmacokinetic parameters and evaluate the bioequivalence of the two formulations.Results The main pharmacokinetic parameters of glipizide in the fasted state were as follows:Cmax were(551.60±91.26)and(518.10±105.10)ng·mL-1;AUC0-t were(3 074.33±861.91)and(3 026.77±934.25)h·ng·mL-1;AUC0-∞ were(3 204.85±990.78)and(3 166.35±1 107.36)h ng·mL-1.The parameters of glipizide in the fed state were as follows:Cmax were(517.30±98.97)and(472.80±114.48)ng·mL-1;AUC0-t were(3 001.12±830.87)and(2 932.79±736.35)h·ng·mL-1;AUC0-∞ were(3 067.00±918.84)and(2 997.44±819.14)h·ng·mL-1.The 90％confidence interval of the Cmax,AUC0-t and AUC0-∞ of the test formulation and the reference formulation were from 80.00％to 125.00％.The incidence of adverse events in fasted group and fed group was no serious adverse events.Conclusion The two glipizide tablets were bioequivalent under fasted and fed conditions,and good security.

Objective: To analyze the impact of parental sports concept and behavior on physical activity in preschool children, so as to provide a foundation for future guidance on fostering childrens physical activity within the family context. Methods: From November to December 2020, a clustered convenience sampling method was employed to conduct surveys, and a total of 283 children were selectal from one kindergarten each in Beijing, Shenyang, and Xian. Participating children wore ActiGraph GT9X accelerometers continuously for one week to collect data on different intensity levels of physical activity. Physical Activity afterschool Questionnaire for Preschooler (P-PAQ) was utilized to assess parental sports concept and behavior. The gender differences in physical activity level and physical activity compliance rate were analyzed by using ttest, Mann-Whitney U test, and Chisquare test; and the relationship between parental exercise concepts and behaviors and physical activity of preschool children was analyzed using Spearman rank correlation analysis and multiple linear regression analysis. Results: Parental sports concept was significantly positively correlated with average daily moderatetovigorous physical activity (MVPA) and total physical activity (TPA) in children (r=0.12-0.16, P<0.05). Parental sports behavior was significantly positively correlated with childrens average daily TPA (r=0.25, P<0.05). Multiple linear regression revealed that parental sports concept was positively correlated with average daily MVPA and TPA in both boys and girls (B=0.65-0.83), while parental sports behavior only was positively correlated with boys average daily MVPA and TPA (B=0.24-0.25)(P<0.05). Conclusions Parental sports concept and behavior can impact physical activity levels in preschool children, exhibiting gender differences. Future guidance on physical activity in family upbringing should consider both parental sports concept and behavior, and pay attention to the influence of childrens gender.

Objective:To explore the clinical and electrophysiological characteristics of peripheral neuropathy in prediabetic patients.Methods:Subjects aged 20-65 years with high-risk factors of impaired glycemia enrolled in Beijing Tiantan Hospital, Capital Medical University from 2019 to 2022 were recruited to conduct oral glucose tolerance test, after excluding other causes of neuropathy or radiculopathy. Patients with impaired fasting glucose or impaired glucose tolerance were defined by American Diabetes Association criteria. These patients were divided into clinical polyneuropathy (PN) and clinical non-PN groups, according to the 2010 Toronto consensus criteria and the presence of PN symptoms and signs or not. Nerve conduction studies (NCS), F wave, sympathetic skin response (SSR), R-R interval variation (RRIV) and current perception thresholds (CPT) were performed and the abnormal rate was compared between different electrodiagnostic methods and between clinical subgroups.Results:Among the 73 prediabetic patients ultimately enrolled, only 20 (27.4%) can be diagnosed as clinical PN according to the Toronto consensus criteria. The abnormal rate of CPT (68.5%, 50/73) was significantly higher than those of F wave (2.7%, 2/73), lower limb NCS (0, 0/73), upper limb NCS changes of carpal tunnel syndrome (26.0%, 19/73), SSR (6.8%, 5/73) and RRIV (5.5%, 4/73; McNemar test, all P<0.001). With sinusoid-waveform current stimuli at frequencies of 2 000 Hz, 250 Hz and 5 Hz, the CPT device was used to measure cutaneous sensory thresholds of large myelinated, small myelinated and small unmyelinated sensory fibers respectively. CPT revealed a 21.9% (16/73) abnormal rate of unmyelinated C fiber in the hands of prediabetic patients, significantly higher than that of large myelinated Aβ fibers [8.2% (6/73), χ2=5.352, P=0.021]. Both abnormal rates of small myelinated Aδ [42.5% (31/73)] and unmyelinated C fibers [39.7% (29/73)] in the feet of prediabetic patients were significantly higher than that of large myelinated Aβ fibers [11.0% (8/73), χ2=18.508, 15.965, both P<0.001]. Compared with the clinical non-PN group, the abnormal rates of CPT [90.0% (18/20) vs 60.4% (32/53), χ2=5.904, P=0.015] and SSR [20.0% (4/20) vs 1.9% (1/53), P=0.016) were significantly higher in the clinical PN group. Conclusions:Peripheral neuropathies in prediabetic patients are usually asymptomatic or subclinical, and predispose to affect unmyelinated and small myelinated sensory fibers. Selective electrodiagnostic measurements of small fibers help to detect prediabetic neuropathies in the earliest stages of the disease.