BACKGROUND:Facet joint osteoarthritis is acknowledged as a significant contributor to lower back pain in the geriatric population.The advent of an innovative spinal facet joint fusion device presents a therapeutic option for intervening during the initial stages of facet joint osteoarthritis,and significantly reduces the incidence of a series of complications caused by poor early conservative treatment and late surgical treatment.However,its effect on the biomechanics of the lumbar spine is unknown.OBJECTIVE:To investigate the biomechanical disparities between the novel lumbar zygapophyseal joint fusion device and traditional fusion devices.METHODS:A comprehensive three-dimensional finite element model of the L3-S1 lumbar spine was established and validated.Based on this intact model,three groups of surgical models were constructed:a bilateral pedicle screw fixation model,a bilateral novel facet joint fusion fixation model,and a bilateral facet screw fixation model,with the surgical segment designated as L4-5.Under a load of 500 N,a torque of 7.5 Nm was applied to all lumbar models to calculate the range of motion,displacement values,and intervertebral disc stress values at the L4-5 segment;stress values at the L3-4 and L5-S1 segments were also measured.RESULTS AND CONCLUSION:(1)Compared with the intact model,the range of motion at the L4-5 segment was reduced in all surgical models.(2)The novel device exhibited the smallest range of motion at the L4-5 segment under left and right rotational conditions;the greatest range of motion at the L4-5 segment under extension conditions;and a greater range of motion under other conditions than the bilateral pedicle screw fixation model.(3)The novel device demonstrated the smallest displacement values at the L4-5 segment under left and right rotational conditions;under other conditions,the displacement values at the L4-5 segment were greater than those in the bilateral pedicle screw fixation model.(4)In terms of stress distribution at the L4-5 segment,the novel device consistently exhibited the smallest values across all conditions.(5)For the L3-4 segment,the novel device showed the greatest stress values under extension and left and right rotational conditions,while under other conditions,the values were lower than those in the bilateral pedicle screw fixation model.(6)Compared with pedicle screw fixation,the novel device produced smaller stress values at the L5-S1 segment.(7)This study indicates that,compared with pedicle screw fixation,the novel device impacts the biomechanics of the lumbar spine by fusing the facet joints.It provides stability while preserving the range of motion at the surgical segment and reduces stress on the intervertebral discs of the surgical and adjacent segments,thereby potentially delaying disc degeneration.This suggests that the novel device can achieve biomechanical effects similar to those of pedicle screw fixation in theory.

Function-preserving gastrectomy has been gradually implemented in China. Under the premise of oncologic safety,such surgery is crucial for improving patients′ postoperative quality of life. Although proximal gastrectomy is a classic surgical method for the adenocarcinoma of esophagogastric junction,no consensus exists on the vagus nerve preservation and digestive tract reconstruction. How to preserve the vagus nerve and pyloric function, and avoid postoperative gastroesophageal reflux after proximal gastrectomy has consistently been the focus of clinical research on proximal gastrectomy. This study introduces the application of laparoscopic proximal gastrectomy with nerve vagus preservation combined with double-flap anastomosis in proximal early gastric cancer. The hepatic branches and the celiac branches are both preserved during the surgical procedure,and the manufacture of double-flap is completed through auxiliary incisions. The anastomosis of the esophagus and the remnant stomach is performed under laparoscopy. It conforms to the physiological structure and preserved the functions of the stomach,which avoided weight loss and nutritional absorption disorder after total gastrectomy. Additionally, it reduces the incidence of reflux esophagitis following traditional esophagogastrostomy, thereby improving patients′ postoperative quality of life.

The surgical management of gastroesophageal reflux disease has evolved significantly with the increased understanding of the physiology of the reflux barrier. Initially, emphasis was on reduction of hiatal hernias and crural closure. With persistence of reflux symptoms, along with the development of esophageal manometry and the discovery of a high-pressure zone, focus evolved to surgical augmentation of the lower esophageal sphincter, including reconstruction of the angle of His, ensuring sufficient intra-abdominal esophageal length, fundoplication, and magnetic sphincter augmentation. More recently, the role of crural closure in antireflux and hiatal hernia repair has again received renewed attention due to the persistence of postoperative complications and recurrences. Rather than simply preventing transthoracic herniation of the fundoplication as was originally thought, crural closure has been documented to have a critical role in re-establishing intra-abdominal esophageal length and maintaining the pressure of LES. The application of mesh provides more options for strengthening crural closure. In this review, this article will discuss the evolution of surgical techniques for gastroesophageal reflux disease over the past century, aiming to better guide the surgical treatment and clinical research of gastroesophageal reflux disease.

Gastric cancer is one of the most common malignancies worldwide. The capacity for invasion and metastasis, as well as high heterogeneity, are the main reasons that gastric cancer patients lose the opportunity for surgery and have a poor prognosis. Despite the rapid advancement of molecular targeted therapies, such as HER2 and immune checkpoint inhibitors, survival of gastric cancer patients is still unsatisfactory because the understanding of the mechanism of gastric cancer progression is still incomplete. Recently, genomic research has critically deepened our knowledge of which gene products are dysregulated in invasive gastric cancer. Furthermore, the study of the interaction of gastric cancer cells with the tumor microenvironment has emerged as a principal subject in driving invasion and metastasis. These results are expected to provide a profound knowledge of how biological molecules are implicated in gastric cancer development. This review will summarize the advances in our current understanding of the molecular mechanism of gastric cancer invasion. Compared to conventional therapy using protease or molecular inhibitors alone, multi-therapy targeting invasion plasticity may seem to be an assuring direction for the progression of novel strategies.

Complement C3 plays a critical role in periodontitis. However, its source, role and underlying mechanisms remain unclear. In our study, by analyzing single-cell sequencing data from mouse model of periodontitis, we identified that C3 is primarily derived from periodontal fibroblasts. Subsequently, we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis. C3ar^-/- mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice, characterized by mild gingival tissue damage and reduced alveolar bone loss. This reduction was associated with decreased production of pro-inflammatory mediators and reduced osteoclast infiltration in the periodontal tissues. Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation. Finally, by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis, we found that the results observed in mice were consistent with human data. Therefore, our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis, driven by macrophage M1 polarization and osteoclast differentiation. These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.
Animals ; Osteoclasts/cytology* ; Periodontitis/metabolism* ; Cell Differentiation ; Mice ; Fibroblasts/metabolism* ; Macrophages ; Disease Models, Animal ; Complement C3/metabolism* ; Humans ; Disease Progression ; Mice, Inbred C57BL ; Male ; Mice, Knockout

BACKGROUND:Facet joint osteoarthritis is acknowledged as a significant contributor to lower back pain in the geriatric population.The advent of an innovative spinal facet joint fusion device presents a therapeutic option for intervening during the initial stages of facet joint osteoarthritis,and significantly reduces the incidence of a series of complications caused by poor early conservative treatment and late surgical treatment.However,its effect on the biomechanics of the lumbar spine is unknown.OBJECTIVE:To investigate the biomechanical disparities between the novel lumbar zygapophyseal joint fusion device and traditional fusion devices.METHODS:A comprehensive three-dimensional finite element model of the L3-S1 lumbar spine was established and validated.Based on this intact model,three groups of surgical models were constructed:a bilateral pedicle screw fixation model,a bilateral novel facet joint fusion fixation model,and a bilateral facet screw fixation model,with the surgical segment designated as L4-5.Under a load of 500 N,a torque of 7.5 Nm was applied to all lumbar models to calculate the range of motion,displacement values,and intervertebral disc stress values at the L4-5 segment;stress values at the L3-4 and L5-S1 segments were also measured.RESULTS AND CONCLUSION:(1)Compared with the intact model,the range of motion at the L4-5 segment was reduced in all surgical models.(2)The novel device exhibited the smallest range of motion at the L4-5 segment under left and right rotational conditions;the greatest range of motion at the L4-5 segment under extension conditions;and a greater range of motion under other conditions than the bilateral pedicle screw fixation model.(3)The novel device demonstrated the smallest displacement values at the L4-5 segment under left and right rotational conditions;under other conditions,the displacement values at the L4-5 segment were greater than those in the bilateral pedicle screw fixation model.(4)In terms of stress distribution at the L4-5 segment,the novel device consistently exhibited the smallest values across all conditions.(5)For the L3-4 segment,the novel device showed the greatest stress values under extension and left and right rotational conditions,while under other conditions,the values were lower than those in the bilateral pedicle screw fixation model.(6)Compared with pedicle screw fixation,the novel device produced smaller stress values at the L5-S1 segment.(7)This study indicates that,compared with pedicle screw fixation,the novel device impacts the biomechanics of the lumbar spine by fusing the facet joints.It provides stability while preserving the range of motion at the surgical segment and reduces stress on the intervertebral discs of the surgical and adjacent segments,thereby potentially delaying disc degeneration.This suggests that the novel device can achieve biomechanical effects similar to those of pedicle screw fixation in theory.

Function-preserving gastrectomy has been gradually implemented in China. Under the premise of oncologic safety,such surgery is crucial for improving patients′ postoperative quality of life. Although proximal gastrectomy is a classic surgical method for the adenocarcinoma of esophagogastric junction,no consensus exists on the vagus nerve preservation and digestive tract reconstruction. How to preserve the vagus nerve and pyloric function, and avoid postoperative gastroesophageal reflux after proximal gastrectomy has consistently been the focus of clinical research on proximal gastrectomy. This study introduces the application of laparoscopic proximal gastrectomy with nerve vagus preservation combined with double-flap anastomosis in proximal early gastric cancer. The hepatic branches and the celiac branches are both preserved during the surgical procedure,and the manufacture of double-flap is completed through auxiliary incisions. The anastomosis of the esophagus and the remnant stomach is performed under laparoscopy. It conforms to the physiological structure and preserved the functions of the stomach,which avoided weight loss and nutritional absorption disorder after total gastrectomy. Additionally, it reduces the incidence of reflux esophagitis following traditional esophagogastrostomy, thereby improving patients′ postoperative quality of life.

Objective To explore the impact of exercise intervention on the reading abilities of chil-dren with Chinese developmental dyslexia(CDD).Methods Twenty-seven CDD children were recruited from patients of Peking University Sixth Hospital,and randomly divided into a CDD exercise interven-tion group of 14 and a CDD control group of 13.Another 14 age-matched normal children were select-ed into a normal control group.All groups kept daily physical activities in school,while the CDD ex-ercise intervention group additionally underwent 8-week individualized gross and fine motor interven-tion.The literacy,reading fluency and reading comprehension of all groups were evaluated by using"Elementary School Students'Literacy Test and Evaluation Scale",one-minute word reading and ele-mentary school students'reading ability assessment.Results Before the intervention,there were no sig-nificant differences between the exercise intervention and control groups in the literacy level,reading fluency,and reading comprehension(P>0.05),which were all significantly lower than the normal con-trol group(P<0.05).However,after the intervention,significant improvement was observed in the aver-age literacy level,reading fluency,and reading comprehension of the CDD exercise intervention group,and the literacy and reading fluency of the CDD control group,as well as the average literacy level and reading comprehension of the normal control group.Moreover,there were no significant differ-ences between the CDD exercise intervention and control groups in the average literacy level and read-ing fluency score(P>0.05),both significantly lower than the normal control group(P<0.05).Mean-while,the reading comprehension score of the CDD exercise intervention group was significantly higher than the CDD control group(P<0.05),but significantly lower than the normal control group(P<0.05).Conclusion Eight-week targeted gross and fine motor intervention can effectively improve reading abili-ty of DD children,especially their reading comprehension.

Purpose: The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). Materials and Methods: An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. Results: Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. Conclusion Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.