1.Effect and mechanism of endoclip papilloplasty in reducing the incidence of cholelithiasis.
Yao LI ; Xiaofang LU ; Yingchun WANG ; Hong CHANG ; Yaopeng ZHANG ; Wenzheng LIU ; Wei ZHENG ; Xiue YAN ; Yonghui HUANG
Chinese Medical Journal 2025;138(20):2596-2603
BACKGROUND:
Endoscopic sphincterotomy (EST) is widely used to treat common bile duct stones (CBDS); however, long-term studies have revealed the increasing incidence of recurrent CBDS after EST. Loss of sphincter of Oddi function after EST was the main cause of recurrent CBDS. Reparation of the sphincter of Oddi is therefore crucial. This study aims to investigate the effectiveness and safety of endoclip papilloplasty (ECPP) for repairing the sphincter of Oddi and elucidate its mechanism.
METHODS:
Eight healthy Bama minipigs were randomly divided into the EST group and the ECPP group at a 1:1 ratio, and bile samples were collected before endoscopy and 6 months later. All minipigs underwent transabdominal biliary ultrasonography for the diagnosis of cholelithiasis 6 months after endoscopy. The biliary microbiota composition and alpha and beta diversity were analyzed by 16S ribosomal RNA gene sequencing. Differential metabolites were analyzed by bile acid metabolomics to explore the predictive indicators of cholelithiasis.
RESULTS:
Three minipigs were diagnosed with cholelithiasis in the EST group, while none in the ECPP group showed cholelithiasis. The biliary Firmicutes/Bacteroidota (F/B) ratio was increased after EST and decreased after ECPP. The Chao1 and observed species index significantly decreased 6 months after EST ( P = 0.017 and 0.018, respectively); however, the biliary α-diversity was similar before and 6 months after ECPP. The β-diversity significantly differed in the EST group before and 6 months after EST, as well as in the ECPP group before and 6 months after ECPP (analysis of similarities [ANOSIM]: R = 0.917, P = 0.040; R = 0.740, P = 0.035; respectively). Glycolithocholic acid (GLCA) and taurolithocholic acid (TLCA) accumulated in bile 6 months after EST.
CONCLUSIONS
ECPP has less impact on the biliary microenvironment than EST and prevents duodenobiliary reflux by repairing the sphincter of Oddi. The bile levels of GLCA and TLCA may be used to predict the risk of cholelithiasis.
Animals
;
Swine, Miniature
;
Swine
;
Cholelithiasis/prevention & control*
;
Sphincterotomy, Endoscopic/methods*
;
Sphincter of Oddi/surgery*
;
Female
;
Male
2.Arsenic trioxide preconditioning attenuates hepatic ischemia- reperfusion injury in mice: Role of ERK/AKT and autophagy.
Chaoqun WANG ; Hongjun YU ; Shounan LU ; Shanjia KE ; Yanan XU ; Zhigang FENG ; Baolin QIAN ; Miaoyu BAI ; Bing YIN ; Xinglong LI ; Yongliang HUA ; Zhongyu LI ; Dong CHEN ; Bangliang CHEN ; Yongzhi ZHOU ; Shangha PAN ; Yao FU ; Hongchi JIANG ; Dawei WANG ; Yong MA
Chinese Medical Journal 2025;138(22):2993-3003
BACKGROUND:
Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI.
METHODS:
In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy.
RESULTS:
A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent.
CONCLUSION
Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals
;
Arsenic Trioxide
;
Autophagy/physiology*
;
Reperfusion Injury/prevention & control*
;
Mice
;
Male
;
Proto-Oncogene Proteins c-akt/physiology*
;
Arsenicals/therapeutic use*
;
Oxides/therapeutic use*
;
Liver/metabolism*
;
Extracellular Signal-Regulated MAP Kinases/metabolism*
;
Mice, Inbred C57BL
3.Research progress on the effects of sedentary behavior and physical activity on diabetes mellitus.
Qi CHEN ; Chuan-Fen LI ; Wen JING
Acta Physiologica Sinica 2025;77(1):62-74
Diabetes mellitus (DM) has become one of the most serious and common chronic diseases around the world, leading to various complications and a reduction in life expectancy. Increased sedentary behavior (SB) and decreased physical activity (PA) are important contributors to the rising prevalence of DM. This article reviews the research progress on the pathogenesis of DM, the effects of SB and PA on the risk of DM, aiming to explore the influence of different PA intensities, amounts, frequencies, durations and types on the incidence of DM. Research has shown that blood glucose levels tend to increase with the prolongation of SB. Within a certain range, PA intensity and amount are negatively correlated with the risk of DM; Performing PA for more than 3 days per week maintains normal glucose tolerance and lower blood pressure; Engaging in 150-300 min of moderate-intensity exercise or 75-150 min of high-intensity exercise per week reduces the risk of DM; PA during leisure time reduces the risk of DM, while PA during work increases the risk of DM; Both aerobic training and resistance training reduce the risk of DM, and the combination of the two training methods produces better benefits; Various types of exercises, such as cycling, soccer, aerobics, yoga and tai chi, all reduce the risk of DM. In summary, prolonged SB increases the risk of DM, while appropriate PA reduces the risk of DM. As the intensity, amount, and frequency of PA increase, the effect of reducing DM risk becomes more significant. Different exercise methods have different effects on reducing DM risk.
Humans
;
Sedentary Behavior
;
Exercise/physiology*
;
Diabetes Mellitus/prevention & control*
6.Risk assessment tools for 0-6 years old children unintentional injuries: A systematic literature analysis.
Yang YUAN ; Li LI ; Guoqing HU
Journal of Central South University(Medical Sciences) 2025;50(1):130-142
OBJECTIVES:
Injuries are the leading cause of death among children and adolescents. Although numerous risk assessment tools for unintentional injuries in children have been developed and published both domestically and internationally, there is currently no global consensus on standardized use. This study aims to systematically characterize existing unintentional injury risk assessment tools for children aged 0-6 years, with the goal of informing scientific tool selection and optimization.
METHODS:
Relevant literature published up to January 2025 was retrieved from CNKI, Wanfang, PubMed, and Web of Science. An information extraction form was developed to gather data on the basic features of each assessment tool, assessment format, scoring methods and criteria, dimensions assessed, reliability and validity, and types of unintentional injuries covered.
RESULTS:
A total of 50 risk assessment tools for unintentional injuries among children aged 0-6 years were included. Among them, 35 tools assessed two or more types of unintentional injuries. Regarding assessment format, 38 tools relied on caregiver self-report, 2 on investigator interviews, 3 on direct observation by investigators, and 7 used multiple methods. The tools covered four major dimensions: knowledge, attitude, behavior, and environment. Eleven tools covered 3 dimensions, while only one tool addressed all 4. Nineteen tools provided clear scoring methods, 14 included criteria for risk determination, and only 11 had both scoring methods and risk criteria. Twenty-eight tools lacked both. Twenty-two tools had been evaluated for reliability and/or validity. Among the 25 English-language tools, only 3 had been translated into Chinese.
CONCLUSIONS
Currently, no existing tool comprehensively assesses all major types of unintentional injuries for children under six years of age. It is recommended that practitioners select appropriate tools based on specific needs. In addition, improvements should be pursued, such as translating and validating English-language tools, developing quantitative scoring methods and criteria for tools tailored to Chinese children for important but underrepresented injury types (e.g., road traffic injuries, drowning).
Humans
;
Infant
;
Child, Preschool
;
Child
;
Risk Assessment/methods*
;
Accidental Injuries/prevention & control*
;
Infant, Newborn
;
Wounds and Injuries/epidemiology*
;
Reproducibility of Results
7.Kazinol B alleviates hypoxia/reoxygenation-induced hepatocyte injury by inhibiting the JNK signaling pathway.
Yi ZHU ; Junhui LI ; Min YANG ; Pengpeng ZHANG ; Cai LI ; Hong LIU
Journal of Central South University(Medical Sciences) 2025;50(2):181-189
OBJECTIVES:
Hypoxia/reoxygenation (H/R) injury is a critical pathological process during liver transplantation. Kazinol B has known anti-inflammatory, anti-apoptotic, and metabolic regulatory properties, but its protective mechanism in H/R-induced liver injury remains unclear. This study aims to investigate the protective effects and underlying mechanisms of Kazinol B in H/R-induced hepatocyte injury.
METHODS:
An ischemia-reperfusion model was established in healthy adult male Sprague-Dawley rats, and an in vitro H/R model was created using cultured hepatocytes. Hepatocytes were treated with Kazinol B (0-100 μmol/L) to assess cytotoxicity and protective effects. Cell viability was evaluated using the cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assays. Expression of apoptosis-related proteins, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad), and cleaved caspase-3, was detected by Western blotting. Reactive oxygen species (ROS) levels were assessed via fluorescence probes, and inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured using enzyme-linked immunosorbent assay (ELISA). TdT-mediated nick end labeling (TUNEL) staining was performed to assess DNA damage and apoptosis.
RESULTS:
Kazinol B had no significant effect on hepatocyte viability at 0-50 μmol/L, but showed cytotoxicity at 100 μmol/L (P<0.05). At 0.1-20 μmol/L, Kazinol B significantly improved cell survival, reduced LDH release, decreased apoptosis, and attenuated DNA damage (all P<0.001). At 10 μmol/L, Kazinol B markedly down-regulated Bad and cleaved caspase-3 (both P<0.05), and up-regulated Bcl-2 (P<0.01). It also dose-dependently reduced ROS levels and inflammatory cytokines TNF-α and IL-1β (all P<0.01). Both in vitro and in vivo, Kazinol B inhibited activation of the c-Jun N-terminal kinase (JNK) pathway without affecting extracellular regulated protein kinase (ERK) signaling (P>0.05). TUNEL staining showed that the protective effect of Kazinol B against apoptosis was partially reversed by the JNK agonist anisomycin (P<0.01).
CONCLUSIONS
Kazinol B mitigates hepatocyte injury induced by H/R by inhibiting the JNK signaling pathway. Its protective effect is associated with suppression of oxidative stress and inflammation, indicating its potential as a hepatoprotective agent.
Animals
;
Hepatocytes/pathology*
;
Rats, Sprague-Dawley
;
Male
;
Rats
;
Reperfusion Injury/prevention & control*
;
Apoptosis/drug effects*
;
Reactive Oxygen Species/metabolism*
;
MAP Kinase Signaling System/drug effects*
;
Cell Survival/drug effects*
;
Cell Hypoxia
;
Cells, Cultured
8.Key techniques of laparoscopic Roux-en-Y gastric bypass.
Zeyang WANG ; Zhi SONG ; Weizheng LI ; Pengzhou LI ; Shaihong ZHU ; Liyong ZHU
Journal of Central South University(Medical Sciences) 2025;50(2):251-258
Bariatric and metabolic surgery has become a primary treatment for decompensated obesity, with the number of procedures rapidly increasing in China in recent years. Various improved and novel surgical techniques have emerged. Given the characteristics of the Chinese obese population lower body mass index compared to Western populations and frequent pancreatic islet dysfunction laparoscopic Roux-en-Y gastric bypass remains one of the mainstream procedures in China. Although the Procedural Guideline for Laparoscopic Roux-en-Y Gastric Bypass (2019 Edition) has provided standardized surgical steps, mastering and routinely implementing the procedure in clinical practice continues to pose significant challenges. Compared to laparoscopic sleeve gastrectomy, laparoscopic Roux-en-Y gastric bypass is more technically demanding and requires a longer learning curve. To avoid suboptimal weight loss or severe postoperative complications resulting from non-standardized techniques, this article summarizes the authors' clinical experience, emphasizing key technical steps: creation of the gastric pouch, standardization of gastrojejunal and jejunojejunal anastomoses, hiatal closure, and full serosalization. These insights aim to improve procedural safety and therapeutic efficacy by offering a set of practical process optimization strategies.
Humans
;
Gastric Bypass/methods*
;
Laparoscopy/methods*
;
Obesity, Morbid/surgery*
;
Postoperative Complications/prevention & control*
;
China
;
Jejunum/surgery*
;
Gastrectomy/methods*
;
Anastomosis, Surgical/methods*
;
Weight Loss
9.Optimization of flow rate and orientation of outflow graft at implantation for patients with left ventricular assist device.
Yongyi WANG ; Li SHI ; Shijun HU ; Xiao TAN ; Tianli ZHAO
Journal of Central South University(Medical Sciences) 2025;50(3):457-468
OBJECTIVES:
A ventricular assist device (VAD) is an electromechanical device used to assist cardiac blood circulation, which can be employed for the treatment of end-stage heart failure and is most commonly placed in the left ventricle. Despite enhancing perfusion performance, the implantation of left ventricular assist device (LVAD) transforms the local intraventricular flow and thus may increase the risk of thrombogenesis. This study aims to investigate fluid-particle interactions and thromboembolic risk under different LVAD configurations using three-dimensional (3D) reconstruction models, focusing on the effects of outflow tract orientation and blood flow rates.
METHODS:
A patient-specific end-diastolic 3D reconstruction model was initially constructed in stereo lithography (STL) format using Mimics software based on CT images. Transient numerical simulations were performed to analyze fluid-particle interactions and thromboembolic risks for LVAD with varying outflow tract orientations under 2 flow rates (4 L/min and 5 L/min), using particles of uniform size (2 mm), and a blood flow rate optimization protocol was implemented for this patient.
RESULTS:
When the LVAD flow rate was 5 L/min, helicity and flow stagnation of the blood flow increased the particle residence time (RT) and the risk of thrombogenesis of the aortic root. The percentage of particles traveling toward the brachiocephalic trunk was up to 20.33%. When the LVAD flow rate was 4 L/min, blood turbulence in the aorta was reduced, the RT of blood particles was shortened, and then the percentage of particles traveling toward the brachiocephalic trunk decreased to 10.54%. When the LVAD blood flow rate was 5 L/min and the direction of the outflow pipe was optimal, the RT of blood particles was shortened, and then the percentage of particles traveling toward the brachiocephalic trunk decreased to 11.22%. A 18-month follow-up observation of the patient revealed that the LVAD was in good working order and the patient had no complications related to the implantation of LVAD.
CONCLUSIONS
Implantation of LVAD results in a higher risk of cerebral infarction; When implanting LVAD with the same outflow tract direction, optimizing flow velocity and outflow tract can reduce the risk of cerebral infarction occurrence.
Heart-Assist Devices/adverse effects*
;
Humans
;
Heart Failure/physiopathology*
;
Blood Flow Velocity
;
Thromboembolism/prevention & control*
;
Models, Cardiovascular
;
Heart Ventricles/physiopathology*
;
Imaging, Three-Dimensional
10.BTVT ameliorates offspring blood-brain barrier damage induced by prenatal and lactational neodymium oxide exposure via the gut-brain axis.
Xiaoyan DU ; Xiaocheng GAO ; Jing CAO ; Xin ZHAO ; Zhi HUO ; Shaoqing ZHAO ; Qingqing LIANG ; Lei GAO ; Yang DENG
Journal of Central South University(Medical Sciences) 2025;50(4):615-624
OBJECTIVES:
Exposure to rare earth elements (REEs) has been linked to various systemic diseases, but their impact on the offspring blood-brain barrier (BBB) via the gut-brain axis remains unclear. This study aims to investigate the effects of maternal exposure to neodymium oxide (Nd2O3) on the BBB integrity of offspring rats, and to evaluate the potential protective role of bifidobacterium tetrad viable tablets (BTVT) against Nd2O3-induced intestinal and BBB damage.
METHODS:
Healthy adult SD rats were mated at a 1:1 male-to-female ratio, with the day of vaginal plug detection marked as gestational day 0. A total of 60 pregnant rats were randomly assigned to the following groups: Control, 50 mg/(kg·d) Nd2O3, 100 mg/(kg·d) Nd2O3, 200 mg/(kg·d) Nd2O3, and 200 mg/(kg·d) Nd2O3 + BTVT group. Treatments were administered by daily oral gavage throughout pregnancy and lactation. On postnatal day 21 (weaning), offspring feces, brain, and colon tissues were collected. Hematoxylin and eosin (HE) staining was used to assess structural changes in brain and intestinal tissues. Short-chain fatty acids (SCFAs) in feces were quantified by gas chromatography-mass spectrometry (GC-MS). Evans Blue (EB) dye extravasation assessed BBB permeability. Gene and protein expression levels of tight junction proteins occludin and zonula occludens-1 (ZO-1) were measured by reverse transcription PCR (RT-PCR) and Western blotting (WB), respectively. Neodymium levels in brain tissue were determined via inductively coupled plasma mass spectrometry (ICP-MS).
RESULTS:
HE staining revealed that maternal Nd2O3 exposure caused mucosal edema, increased submucosal spacing, and lymphocyte infiltration in offspring colon, as well as neuronal degeneration and vacuolization in brain tissue. BTVT intervention alleviated these changes. GC-MS analysis showed that levels of acetic acid, propionic acid, butyric acid, and isobutyric acid significantly decreased, while valeric acid and isovaleric acid increased in offspring of Nd2O3-exposed mothers (P<0.05). BTVT significantly restored levels of acetic, propionic, and isobutyric acids and reduced valeric acid content (P<0.05). EB permeability was significantly elevated in Nd2O3-exposed offspring brains (P<0.05), but reduced with BTVT treatment (P<0.05). RT-PCR and WB showed downregulation of occludin and ZO-1 expression following Nd2O3 exposure (P<0.05), which was reversed by BTVT (P<0.05). ICP-MS results indicated significantly increased brain neodymium levels in offspring from all Nd2O3-exposed groups (P<0.05), while BTVT significantly reduced neodymium accumulation compared to the 200 mg/(kg·d) Nd2O3 group (P<0.05).
CONCLUSIONS
Maternal exposure to Nd2O3 during pregnancy and lactation disrupts intestinal health and BBB integrity in offspring, elevates brain neodymium accumulation, and induces neuronal degeneration. BTVT effectively mitigates Nd2O3-induced intestinal and BBB damage in offspring, potentially through modulation of the gut-brain axis.
Animals
;
Female
;
Blood-Brain Barrier/pathology*
;
Pregnancy
;
Rats, Sprague-Dawley
;
Rats
;
Male
;
Neodymium/toxicity*
;
Prenatal Exposure Delayed Effects/prevention & control*
;
Lactation
;
Maternal Exposure/adverse effects*
;
Brain

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