Oral squamous cell carcinoma (OSCC) is a malignant tumor that seriously threatens human health. Its typical biological characteristics include strong local invasiveness, high lymph node metastasis rate, and high recurrence rate after treatment. Hepatocyte growth factor (HGF), cellular-mesenchymal to epithelial transition factor (c-Met), and the HGF/c-Met signaling pathway are involved in the regulation of the occurrence and development of OSCC. HGF and c-Met proteins are overexpressed in OSCC, and multiple studies have suggested that they are significantly associated with the malignant characteristics of tumors and poor prognosis. Furthermore, the abnormal activation of the HGF/c-Met signaling pathway (driven by HGF-dependent autocrine/paracrine or non-dependent mechanisms such as MET gene mutations, amplification, fusion, and protein overexpression) can synergistically promote tumor cell invasion, metastasis, and angiogenesis by activating downstream signaling pathways. However, HGF/c-Met can also mediate immune escape by promoting lactate secretion increase, inducing programmed death ligand 1 (PD-L1) expression upregulation, activating and expanding myeloid-derived suppressor cells, and promoting the proliferation of regulatory T cells (Tregs). In addition, the crosstalk between the HGF/c-Met signaling pathway and key pathways such as phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT), epidermal growth factor receptor (EGFR), Janus kinase (JAK)/signal transducer and activator of transcription (STAT3), and non-coding RNAs can also promote tumor progression. Currently, three types of targeted drugs have been developed targeting the HGF/c-Met pathway: HGF monoclonal antibody, c-Met monoclonal antibody, and tyrosine kinase inhibitors. Some of these drugs have entered clinical trials. However, the emergence of drug resistance during treatment, especially the bidirectional compensatory activation of alternative signaling pathways such as EGFR, has become a major challenge in clinical practice. This article aims to provide an in-depth analysis of the mechanism of action of the HGF/c-Met pathway in OSCC and its interaction with other pathways, and to review the current research status of existing therapeutic drugs. The aim is to provide an important theoretical basis for developing more effective combined treatment strategies and achieving individualized precise treatment, ultimately improving the clinical prognosis and quality of life of patients.

Objective To investigate the situation and influencing factors of preserved ratio impaired spirometry (PRISm) among dust-exposed workers in a wooden furniture manufacturing enterprise. Methods A total of 562 dust-exposed workers from a wooden furniture enterprise in Guangdong Province were selected as the study subjects using the convenience sampling method. The result of health-status questionnaire and occupational medical examinations among the participants were studied, and the influencing factors of PRISm were studied using the binary logistic regression analysis method. Results The detection rate of PRISm was 22.1% (124/562) among the study subjects. Binary logistic regression result showed that male workers had a higher risk of PRISm than female workers (P<0.01). Current smokers had a higher risk of PRISm than non-smokers (P<0.05). Workers with longer duration of exposure to occupational hazards had a higher risk of PRISm (P<0.05), those with higher grade of small-airway dysfunction had a higher risk of PRISm (P<0.01). In terms of body mass index, overweight or obese workers showed a higher detection rate of PRISm than those with normal weight (P<0.01). Greater amount of smoking pack per year had a higher risk of PRISm (P<0.01). Conclusion Dust-exposed workers in the wooden furniture manufacturing industry show a relatively high detection rate of PRISm. Male, current smoker, longer duration of exposure to occupational hazards, small airway dysfunction, overweight or obese, and smoking pack per year are influencing factors of PRISm among the dust-exposed workers in the wooden furniture manufacturing industry.

Objective To investigate the safety, efficacy, and clinical value of a fracture reduction and fixation system. Methods The design and application of components [Kirschner wire (K-wire) limiter and K-wire guiding locking device] of the fracture reduction and fixation system were described. Six surgeons implanted K-wires into synthetic bones using the K-wire limiter or by perception respectively, and the length of K-wire protrusion was assessed. K-wire guiding locking device combined with locking plates and two 1.5 mm K-wires, two 1.5 mm K-wires, as well as two 2.0 mm K-wires were used to fix a fracture model constructed by synthetic bones, and the torque at failure was measured. Results The K-wire limiter reduced the length of K-wire protrusion(P < 0.001). The failure torque of fractures fixed by K-wire guiding locking device with locking plates and two 1.5 mm K-wires was larger than those fixed with two 1.5 mm K-wires and two 2.0 mm K-wires(P < 0.05). Conclusion The fracture reduction and fixation system offers a new technique for reducing and reconstructing fractures, assessing and optimizing the position of locking plate screws, as well as protecting the blood supply of fractures.

Objective To analyze the type and incidence of abnormal chromosome karyotype in peripheral blood of infertile patients with different semen quality.Methods Selectet 292 infertility patients who came to our hospital from January 2018 to December 2021 for G-banding karyotyping and semen analysis.According to the semen analysis results,the patients were divided into abnormal semen quality group and normal control group.We made statistics and analysis on the abnormal karyotypes.Results In the group with abnormal semen quality,20 cases(18.87%)of abnormal karyotypes were found.In the normal control group,9 cases(4.84%)had abnormal karyotypes were found.The comparison of the abnormal rates of peripheral blood chromosome karyotypes between the two groups showed statistical significance(P<0.05).The detection rate of chromosomal abnormalities in patients with Azoospermia was 50%,and sex chromosome abnormalities were the main types of abnormalities in this group.Conclusion Karyotype analysis of infertile patients can effectively analyze the causes of infertility,and has important clinical significance for assisted reproduction and primary prevention of birth defects.

With the aging population, the increasing incidence of adult spinal deformity (ASD) associated with osteoporosis (OP) presents new challenges for evaluation and management. Although reasonable and standardized non-surgical treatment remains the first choice in the early stages of this disease, surgical treatment is necessary for patients with severe deformities and significant symptoms to achieve further improvement. Proximal junctional kyphosis/failure (PJK/PJF) is one of the most serious postoperative complications of ASD. Careful and comprehensive preoperative evaluation of bone quality and body sagittal alignment is crucial for the successful implementation of the operation. The Hounsfield unit (HU) based on CT imaging and the vertebral bone quality (VBQ) score based on MRI have proven to be reliable, effective, simple, and widely used in evaluating local vertebral bone quality in recent years. For the evaluation and prediction of PJF after ASD, the bone quality of the upper instrumented vertebra (UIV) can be assessed using HU values to identify high-risk patients and implement preventive measures. The VBQ score is predictive of the incidence of PJK/PJF in patients undergoing ASD surgery, with a high VBQ score being one of the risk factors for PJK/PJF after ASD correction. Patients with high VBQ scores can delay surgery and use anti-osteoporosis drugs before surgery to reduce the occurrence of PJK/PJF. Meanwhile, reasonable and personalized recovery parameters of ASD patients' sagittal sequence can help balance the benefits of efficacy and complications, maximizing the overall benefits. The prevention of PJK/PJF is challenging due to the stress gap between the internal fixation area and the original unfixed tissue area in the postoperative proximal junctional area, which is increasingly significant in OP patients. It is necessary to improve the fixation strength and bone riveting strength of the proximal junction area properly and to gradually decrease the fixed strength in the proximal junctional area to achieve a smooth transition of stress and avoid stress concentration resulting in failure. Relevant strategies include: 1. Enhanced proximal junction fixation, such as vertebral cement-enhanced pedicle screw fixation. 2. Strategies to cushion the stress in the proximal junction, such as Topping-off technology, which includes laminar/transverse hooks, dynamic rods, multi-segment stabilization screws, and multiple ligament-binding straps. 3. Minimally invasive technology can better protect the soft tissues such as the posterior ligament complex and muscles, reduce iatrogenic injury, and thus reduce the incidence of PJK/PJF. Currently, there are many controversies about the optimal treatment for ASD with OP, but the goal is to achieve maximum efficacy while minimizing complications. Additionally, attention should be paid to reasonable and standard anti-osteoporosis treatment in the perioperative period. This paper summarizes the relevant studies used to evaluate PJK/PJF after ASD in patients with OP and reviews the research progress on PJK/PJF prevention strategies, providing reference and ideas for reducing postoperative proximal junctional complications in adult spinal deformity patients with osteoporosis.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

Liver is the central hub regulating energy metabolism during feeding-fasting transition. Evidence suggests that fasting and refeeding induce dynamic changes in liver size, but the underlying mechanisms remain unclear. Yes-associated protein (YAP) is a key regulator of organ size. This study aims to explore the role of YAP in fasting- and refeeding-induced changes in liver size. Here, fasting significantly reduced liver size, which was recovered to the normal level after refeeding. Moreover, hepatocyte size was decreased and hepatocyte proliferation was inhibited after fasting. Conversely, refeeding promoted hepatocyte enlargement and proliferation compared to fasted state. Mechanistically, fasting or refeeding regulated the expression of YAP and its downstream targets, as well as the proliferation-related protein cyclin D1 (CCND1). Furthermore, fasting significantly reduced the liver size in AAV-control mice, which was mitigated in AAV Yap (5SA) mice. Yap overexpression also prevented the effect of fasting on hepatocyte size and proliferation. Besides, the recovery of liver size after refeeding was delayed in AAV Yap shRNA mice. Yap knockdown attenuated refeeding-induced hepatocyte enlargement and proliferation. In summary, this study demonstrated that YAP plays an important role in dynamic changes of liver size during fasting-refeeding transition, which provides new evidence for YAP in regulating liver size under energy stress.

Objective:To study the effect of insulin intraperitoneal administration combined with dietary intervention on glycemic regulation in in KKAy mice with spontaneous type 2 diabetes.Methods:An animal model of type 2 diabetes was established, and healthy C57BL/6J mice were selected as the normal control group and healthy KKAy mice as the non-disease group. The successfully modeled KKAy mice were randomly divided into the subcutaneous group, the intraperitoneal group, and the untreated group. The non-disease group was given a maintenance diet, and all other groups were fed a high-fat, high-sugar diet. The daily feeding time was from 08:00 to 20:00, with one feeding at a 4-hour interval, for a total of four times. The subcutaneous and intraperitoneal groups were given subcutaneous and intraperitoneal insulin injections before feeding, and recombinant glargine insulin injection (subcutaneous group: 0.125 IU/g; intraperitoneal group: 0.250 IU/g) was injected before the first feeding, and biosynthetic human insulin injection (subcutaneous group: 0.075 IU/g; intraperitoneal group: 0.125 IU/g) was injected after a 0.5 h interval; the rest 3 times before feeding, the biosynthetic human insulin injection (subcutaneous group: 0.075 IU/g; intraperitoneal group: 0.125 IU/g) was injected for 4 weeks. The dietary intake, body mass, fasting blood glucose, and 1 and 2 h postprandial blood glucose of mice in each group were tested regularly, and an oral glucose tolerance test was performed.Results:The total dietary intake of mice in the intraperitoneal group was lower than that in the subcutaneous group. Compared with the initial body mass, the body mass of the mice in the subcutaneous and intraperitoneal groups decreased by 5.05 and 3.59 g at week 4, respectively. The changes of fasting blood glucose in the subcutaneous and intraperitoneal groups ranged from 5.4 to 9.4 and 5.4 to 6.4 mmol/L, respectively, and the changes of 1 h postprandial blood glucose ranged from 4.6 to 12.3 and 5.7 to 8.9 mmol/L, respectively, and the changes of 2 h postprandial blood glucose ranged from 2.5 to 9.8 and 3.8 to 7.1 mmol/L, respectively. For the glucose tolerance index, the intraperitoneal group showed improvement at all time points, and the subcutaneous group showed a decrease at all time points except for 0 and 60 min.Conclusions:In combination with dietary intervention, insulin intraperitoneal injection was more effective in controlling blood glucose in KKAy mice with spontaneous type 2 diabetes compared with subcutaneous insulin injection, and had a significant improvement in glucose tolerance.

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
Mice ; Animals ; Adipose Tissue, Brown ; Sirtuin 1/pharmacology* ; Diabetes Mellitus, Type 2/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Morus/metabolism* ; Flavonoids/metabolism* ; Prospective Studies ; Signal Transduction ; Adipose Tissue, White ; Plant Leaves ; Uncoupling Protein 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*

Ribosomes are abundant,large RNA-protein complexes that are the sites of all protein synthesis in cells.Defects in ribosomal proteins(RPs),including proteoforms arising from genetic variations,alternative splicing of RNA transcripts,post-translational modifications and alterations of protein expression level,have been linked to a diverse range of diseases,including cancer and aging.Comprehensive character-ization of ribosomal proteoforms is challenging but important for the discovery of potential disease biomarkers or protein targets.In the present work,using E.coli 70S RPs as an example,we first developed a top-down proteomics approach on a Waters Synapt G2 Si mass spectrometry(MS)system,and then applied it to the HeLa 80S ribosome.The results were complemented by a bottom-up approach.In total,50 out of 55 RPs were identified using the top-down approach.Among these,more than 30 RPs were found to have their N-terminal methionine removed.Additional modifications such as methylation,acetylation,and hydroxylation were also observed,and the modification sites were identified by bottom-up MS.In a HeLa 80S ribosomal sample,we identified 98 ribosomal proteoforms,among which multiple truncated 80S ribosomal proteoforms were observed,the type of information which is often overlooked by bottom-up experiments.Although their relevance to diseases is not yet known,the integration of top-down and bottom-up proteomics approaches paves the way for the discovery of proteoform-specific disease biomarkers or targets.