Clinical application of serum CST4 combined with tumor markers in the diagnosis of digestive system malignant tumors.

The aim of the present study was to evaluate the diagnostic value of plasma human cystatin-S (CST4) in patients with digestive system malignant tumors. CST4 and tumor markers, such as α-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA)199, CA125, CA153 and CA724, were detected in blood samples from 100 patients with a digestive system malignant tumor and 100 patients with benign digestive system diseases. The tumor markers AFP, CEA, CA199, CA125, CA153 and CA724 were detected using an electrochemiluminescence immunoassay, and CST4 levels were detected using a human CST4 ELISA kit. The results demonstrated that the sensitivities of AFP and CA153 (both 5.00%) were significantly lower than that of CST4 (38.00%) in the diagnosis of digestive system malignancy (P<0.001), and CA724 (18.00%) was also less sensitive than CST4 (P<0.05). The sensitivities of CA199 (26.00%), CEA (31.00%) and CA125 (25.00%) were similar to that of CST4 (P>0.05). There was no significant difference in the CEA, CA125, CA724 and CST4 specificities (P>0.05), which were 91.00, 95.00, 94.00 and 83.00%, respectively. The specificities of AFP (99.00%), CA199 (98.00%) and CA153 (100.00%) were significantly higher than that of CST4 (P<0.01). By constructing a receiver operating characteristic curve and comparing the area under the curve as well as sensitivity, the findings of the present study demonstrated that combining CST4 with AFP, CEA, CA199, CA125, CA153 and CA724 can significantly enhance the diagnostic sensitivity for malignancies of the digestive system. However, the introduction of CST4 into the traditional diagnostic groups (CEA + AFP, CA199 + CA125 + CA153 + CA724 and AFP + CEA + CA199 + CA125 + CA153 + CA724) resulted in an increased sensitivity and loss of specificity, thereby not offering significant advantages in terms of comprehensive diagnostic efficiency compared with the traditional diagnostic groups. In conclusion, CST4 detection may be a promising diagnostic tool. Nonetheless, the potential false positive results in tumor diagnosis should be taken into consideration when developing new diagnostic groups involving CST4.

Clinical application of serum seven tumour-associated autoantibodies in patients with pulmonary nodules.

Background: The incidence of pulmonary nodules is increasing because of the promotion and popularisation of low-dose computed tomography (LDCT) screening for populations with suspected lung cancer. However, a high rate of false positives and concerns regarding the radiation-related cancer risk of repeated CT scanning remain major obstacles to its wide application. This study aimed to investigate the clinical value of seven tumour-associated autoantibodies (7-TAAbs) in the differentiation of malignant pulmonary tumours from benign ones and the early detection of lung cancer in routine clinical practice. Methods: We included 377 patients who underwent both the 7-TAAbs panel test and LDCT screening, and were diagnosed with pulmonary nodules using LDCT. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels antibodies for P53, PGP9.5, SOX2, GAGE7, GBU4-5, CAGE, and MAGE-A1. The relationships between the positive rates of the 7-TAAbs and the patient sex, and age, and the number, size, and composition of pulmonary nodules were analysed. We then statistically evaluated the clinical application value. Results: The positive rates of the 7-TAAbs did not correlate with sex, age, number, size, or composition of pulmonary nodules. The serum antibody level of GBU4-5 in patients with pulmonary nodules tended to increase with age; the serum antibody level of SOX2 tended to increase with nodule size and was the highest among patients with mixed ground-glass opacity (mGGO) nodules. The antibody positive rate for CAGE in female patients with pulmonary nodules was significantly higher than that in male patients (P < 0.05). The positive rate of GBU4-5 antibody in patients aged 60 years and above was higher than that in younger patients (P < 0.05). The positive rate of GAGE7 antibody in patients with pulmonary nodules sized 8-20 mm was also significantly higher than that in patients with pulmonary nodules sized less than 8 mm (P < 0.01). Significant differences were observed in the GAGE7 antibody levels of patients with pulmonary nodules of different compositions (P < 0.01). The positive rate of the 7-TAAbs panel test in patients with lung cancer was significantly higher than in patients with pulmonary nodules (P < 0.01). Serum levels of P53, SOX2, GBU4-5, and MAGE-A1 antibodies were significantly higher in patients with lung cancer than in those with pulmonary nodules (P < 0.05). Conclusion: The low positive rates of serum 7-TAAbs in patients with lung cancer and pulmonary nodules may be related to different case selection, population differences, geographical differences, different degrees of progression, and detection methods. The combined detection of 7-TAAbs has some clinical value for screening and early detection of lung cancer.

Clinicopathological characteristics and prognosis of Epstein-Barr virus-associated gastric cancer.

OBJECTIVE: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS). METHODS: A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis. RESULTS: Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%. CONCLUSION: EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy.

α-Ketoglutarate for Preventing and Managing Intestinal Epithelial Dysfunction.

The epithelium lining the intestinal tract serves a multifaceted role. It plays a crucial role in nutrient absorption and immune regulation and also acts as a protective barrier, separating underlying tissues from the gut lumen content. Disruptions in the delicate balance of the gut epithelium trigger inflammatory responses, aggravate conditions such as inflammatory bowel disease, and potentially lead to more severe complications such as colorectal cancer. Maintaining intestinal epithelial homeostasis is vital for overall health, and there is growing interest in identifying nutraceuticals that can strengthen the intestinal epithelium. α-Ketoglutarate, a metabolite of the tricarboxylic acid cycle, displays a variety of bioactive effects, including functioning as an antioxidant, a necessary cofactor for epigenetic modification, and exerting anti-inflammatory effects. This article presents a comprehensive overview of studies investigating the potential of α-ketoglutarate supplementation in preventing dysfunction of the intestinal epithelium.

Low-dose radiotherapy synergizes with iRGD-antiCD3-modified T cells by facilitating T cell infiltration.

BACKGROUND AND PURPOSE: Poor penetration of transferred T cells represents a critical factor impeding the development of adoptive cell therapy in solid tumors. We demonstrated that iRGD-antiCD3 modification promoted both T cell infiltration and activation in our previous work. Interest in low-dose radiotherapy has recently been renewed due to its immuno-stimulatory effects including T cell recruitment. This study aims to explore the synergistic effects between low-dose radiotherapy and iRGD-antiCD3-modified T cells. MATERIALS AND METHODS: Flow cytometry was performed to assess the expression of iRGD receptors and chemokines. T cell infiltration was evaluated by immunohistofluorescence and in vivo real-time fluorescence imaging and antitumor effects were investigated by in vivo bioluminescence imaging in the gastric cancer peritoneal metastasis mouse model. RESULTS: We found that 2 Gy irradiation upregulated the expression of all three iRGD receptors and T-cell chemokines. The addition of 2 Gy low-dose irradiation boosted the accumulation and penetration of iRGD-antiCD3-modified T cells in peritoneal tumor nodules. Combining 2 Gy low-dose irradiation with iRGD-antiCD3-modified T cells significantly inhibited tumor growth and prolonged survival in the peritoneal metastasis mouse model with a favorable safety profile. CONCLUSION: Altogether, we demonstrated that low-dose radiotherapy could improve the antitumor potency of iRGD-antiCD3-modified T cells by promoting T cell infiltration, providing a rationale for exploring low-dose radiotherapy in combination of other adoptive T cell therapies in solid tumors.

Synergistic acceleration of machine learning and molecular docking for prostate-specific antigen ligand design.

Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities.

Dietary Cannabidiol Activates PKA/AMPK Signaling and Attenuates Chronic Inflammation and Leaky Gut in DSS-Induced Colitis Mice.

SCOPE: Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gut, accompanied by impaired epithelial integrity, increased macrophage infiltration, and enhanced colon cancer risk. METHODS AND RESULTS: Cannabidiol (CBD), a phytocannabinoid isolated from cannabis plants, is supplemented into mice diet, and its beneficial effects against dextran sulfate sodium (DSS)-induced experimental colitis is evaluated. Eight-week-old mice were fed a standard diet supplemented with or without CBD (200 mg kg-1 ) for 5 weeks. In the 4th week of dietary treatment, mice were subjected to 2.5% DSS induction for 7 days, followed by 7 days of recovery, to induce colitis. CBD supplementation reduced body weight loss, gross bleeding, fecal consistency, and disease activity index. In addition, CBD supplementation protected the colonic structure, promoted tissue recovery, and ameliorated macrophage infiltration in the colonic tissue, which was associated with the activation of cyclic AMP-protein kinase A, extracellular signal-regulated kinase ½, and AMP-activated protein kinase signaling pathways. CBD supplementation also suppressed NLRP3 inflammasome activation and related pro-inflammatory marker secretion. Consistently, CBD feeding reduced tight junction protein claudin2 and myosin light chain kinase in DSS-treated mice. CONCLUSION: Dietary CBD protects against inflammation and colitis symptoms induced by DSS, providing an alternative approach to IBD management.

The Development of Aspergillus flavus and Biosynthesis of Aflatoxin B1 are Regulated by the Golgi-Localized Mn2+ Transporter Pmr1.

Microorganisms rely on diverse ion transport and trace elements to sustain growth, development, and secondary metabolism. Manganese (Mn2+) is essential for various biological processes and plays a crucial role in the metabolism of human cells, plants, and yeast. In Aspergillus flavus, we confirmed that Pmr1 localized in cis- and medial-Golgi compartments was critical in facilitating Mn2+ transport, fungal growth, development, secondary metabolism, and glycosylation. In comparison to the wild type, the Δpmr1 mutant displayed heightened sensitivity to environmental stress, accompanied by inhibited synthesis of aflatoxin B1, kojic acid, and a substantial reduction in pathogenicity toward peanuts and maize. Interestingly, the addition of exogenous Mn2+ effectively rectified the developmental and secondary metabolic defects in the Δpmr1 mutant. However, Mn2+ supplement failed to restore the growth and development of the Δpmr1Δgdt1 double mutant, which indicated that the Gdt1 compensated for the functional deficiency of pmr1. In addition, our results showed that pmr1 knockout leads to an upregulation of O-glycosyl-N-acetylglucose (O-GlcNAc) and O-GlcNAc transferase (OGT), while Mn2+ supplementation can restore the glycosylation in A. flavus. Collectively, this study indicates that the pmr1 regulates Mn2+ via Golgi and maintains growth and metabolism functions of A. flavus through regulation of the glycosylation.

Benzoquinone-Lubricated Intercalation in Manganese Oxide for High-Capacity and High-Rate Aqueous Aluminum-Ion Battery.

Aqueous aluminum-ion batteries are attractive post-lithium battery technologies for large-scale energy storage in virtue of abundant and low-cost Al metal anode offering ultrahigh capacity via a three-electron redox reaction. However, state-of-the-art cathode materials are of low practical capacity, poor rate capability, and inadequate cycle life, substantially impeding their practical use. Here layered manganese oxide that is pre-intercalated with benzoquinone-coordinated aluminum ions (BQ-AlxMnO2) as a high-performance cathode material of rechargeable aqueous aluminum-ion batteries is reported. The coordination of benzoquinone with aluminum ions not only extends interlayer spacing of layered MnO2 framework but reduces the effective charge of trivalent aluminum ions to diminish their electrostatic interactions, substantially boosting intercalation/deintercalation kinetics of guest aluminum ions and improving structural reversibility and stability. When coupled with Zn50Al50 alloy anode in 2 m Al(OTf)3 aqueous electrolyte, the BQ-AlxMnO2 exhibits superior rate capability and cycling stability. At 1 A g-1, the specific capacity of BQ-AlxMnO2 reaches ≈300 mAh g-1 and retains ≈90% of the initial value for more than 800 cycles, along with the Coulombic efficiency of as high as ≈99%, outperforming the AlxMnO2 without BQ co-incorporation.

Dietary purple potato supplement attenuates DSS-induced colitis in mice: impact on mitochondrial function.

Inflammatory bowel disease (IBD) is a condition characterized by disrupted intestinal barrier function, abnormal immune response, and mucosal structure loss. This study evaluated the beneficial role of purple potato (PP) supplementation against IBD symptoms using a murine model of dextran sulfate sodium (DSS)-induced colitis, and further explored the underlying mechanisms. Six-week-old C57BL/6J male mice were randomized into two groups and fed a standard rodent diet with or without 10% PP powder for 7 weeks. At the 5th week of dietary supplements, mice in each group were further divided into two subgroups and were either induced with or without 2.5% DSS induction for 7 days, followed by 7 days of recovery. Data showed that PP supplementation ameliorated the disease activity index in DSS-treated mice and reversed the colonic structure loss, mucosal damage, macrophage infiltration, and pro-inflammatory cytokine secretion induced by DSS in the colonic tissue. PP supplementation also restored the levels of tight junction proteins and caudal type homeobox 2 in DSS-treated mice. Furthermore, dietary PP enhanced peroxisome proliferator-activated receptor-γ coactivator-1α signaling pathway, mitochondrial biogenesis, mitochondrial proteostasis, and protein-folding capacity. In summary, dietary PP ameliorated DSS-induced colitis and improved gut structures and barrier function, which was associated with improved mitochondrial function. These results support further investigation of PP as a potential dietary intervention for IBD.

1,25(OH)2 D3 inhibits Lewis lung cancer cell migration via NHE1-sensitive metabolic reprograming.

High prevalence and metastasis rates are characteristics of lung cancer. Glycolysis provides energy for the development and metastasis of cancer cells. The 1,25-dihydroxy vitamin D3 (1,25(OH)2 D3 ) has been linked to reducing cancer risk and regulates various physiological functions. We hypothesized that 1,25(OH)2 D3 could be associated with the expression and activity of Na+ /H+ exchanger isoform 1 (NHE1) of Lewis lung cancer cells, thus regulating glycolysis as well as migration by actin reorganization. Followed by online public data analysis, Vitamin D3 receptor, the receptor of 1,25(OH)2 D3 has been proved to be abundant in lung cancers. We demonstrated that 1,25(OH)2 D3 treatment suppressed transcript levels, protein levels, and activity of NHE1 in LLC cells. Furthermore, 1,25(OH)2 D3 treatment resets the metabolic balance between glycolysis and OXPHOS, mainly including reducing glycolytic enzymes expression and lactate production. In vivo experiments showed the inhibition effects on tumor growth as well. Therefore, we concluded that 1,25(OH)2 D3 could amend the NHE1 function, which leads to metabolic reprogramming and cytoskeleton reconstruction, finally inhibits the cell migration.

Pediatric Mycotic Pseudoaneurysm of the Ascending Aorta: A Case Report.

Mycotic pseudoaneurysm of the ascending aorta is extremely uncommon, particularly in children with no prior cardiac surgery or trauma. We report a rare case of a mycotic pseudoaneurysm of the ascending aorta in a 2-year-old girl with no history of cardiac surgery. Investigations revealed a methicillin-resistant Staphylococcus aureus infection and significant pericardial effusion in the child who presented with persistent fever and altered mental state. Cardiac ultrasound revealed a disruption in the aortic wall and a tumor-like structure. Contrast-enhanced computed tomography confirmed an ascending aortic pseudoaneurysm with thrombus. The child underwent successful surgical treatment without implants. This case emphasizes the diagnostic significance of imaging, particularly the advantages of ultrasound in pediatric settings, and the need for timely and accurate diagnosis using appropriate imaging modalities in children.

A Case of Postnatal Aortic Arch Atresia.

Background: Aortic arch atresia is a rare congenital cardiac defect that may occur after birth. Pregnant women with gestational diabetes mellitus may increase the risk of aortic arch atresia in newborns after birth. Case Description: A 16-day-old infant was referred to our hospital on the 15th postnatal day after an interrupted or atretic aortic arch was discovered. No obvious abnormality was detected in the infant during the prenatal ultrasound. Laboratory tests showed elevated inflammatory marker levels. Transthoracic echocardiography showed stenosis of the transverse arch of the aorta and a blind end at the distal end of the left subclavian artery. During surgery, it was found that the isthmus of the aorta was uninterrupted but completely occluded due to inflammation. Conclusion: This case demonstrates that type A interrupted aortic arch and coarctation of the aorta can be acquired after birth, and if coarctation of the aorta is complicated by inflammation or if the pregnant women have gestational diabetes mellitus, it can result in aortic arch atresia as the patient's condition worsens. It is advised to consider aortic arch atresia when imaging reveals type A interrupted aortic arch.

Implementation of STRONGkids for identifying nutritional risk in outpatients of child health care clinics: Results of a multicentre study.

AIM: To investigate nutritional risk across children in their first 2 years at child health care clinics in Jiangsu, China, and to highlight the importance of nutritional risk screening in outpatient clinics. METHODS: A multi-centre, cross-sectional, observational study was conducted among outpatients in child health care clinics. Nutritional risk screening using the STRONGkids tool and anthropometric assessments were performed on children under 2 years old at outpatient initial visits in ten hospitals from March 2021 to March 2022. RESULTS: There were 11,454 children enrolled. The percentages of children with high, moderate and low nutritional risk were 2.0% (228), 28.2% (3229) and 69.8% (7997), respectively. The occurrence rate of high nutritional risk was higher in female children than in male children (p < 0.05). The incidence of moderate nutritional risk in infants was significantly higher than in children aged ≥12 months (p < 0.01). Children with moderate or high nutritional risk more frequently answered 'yes' to the STRONGkids item 'high risk disease or major surgery planned'. The top three diagnoses related to nutritional risk were prematurity (50.5%), food allergy (14.3%) and recurrent respiratory disease (10.7%). In addition, the incidence of chronic undernutrition in children with moderate (14.0%) or high nutritional risk (36.4%) was significantly higher than acute undernutrition (p < 0.01). CONCLUSION: Among children up to 2 years of age seen in child health clinics, nutritional risk associated with prematurity and potential disease requires special attention. Nutritional risk screening should be part of child health care, and STRONGkids is a useful screening tool.

The association between thyroid-stimulating hormone and thyroid nodules, goiter and thyroid antibody positivity.

Background: The relationship between normal thyroid-stimulating hormone (TSH) levels and thyroid disease in adults remains controversial. This study aimed to investigate the correlation between serum TSH levels, particularly those falling within the normal range, and thyroid diseases in Chinese adults, including thyroid nodules (TN), goiter (GR), and thyroid antibody positivity. Materials and methods: This research was a cross-sectional study conducted in an adult population in Tianjin, China. Thyroid volume (Tvol) and TN were assessed using thyroid ultrasonography. Fasting venous blood and spot urine samples were collected to evaluate thyroid function and iodine status. Results: A total of 2460 subjects participated in the survey. The prevalence of thyroid dysfunction was 9.76%, and abnormal TSH levels were found to potentially increase the risk of GR and thyroid antibody positivity in adults. A total of 2220 subjects with TSH within the normal reference range were included in the further study. In these patients, Tvol decreased as TSH levels increased, in both men and women (P < 0.0001). Low TSH levels (0.27-1.41 IU/mL) were identified as a risk factor for TN (odds ratio [OR], 1.46; 95% CI: 1.14-1.87) and GR (OR 5.90, 95% CI 2.27-15.3). Upon stratification by sex and age, the risk of TN was found to be higher in women and elderly individuals (≥60 years old), while the risk of GR was found to be higher in men and younger individuals (<60 years old). High TSH levels (2.55-4.2 IU/mL) were identified as a risk factor for thyroid antibody positivity (OR, 1.53; 95% CI: 1.11-2.10). Men and younger individuals with high TSH levels exhibited a higher risk of thyroid antibody positivity. Conclusion: In adults with normal TSH levels, low TSH levels were associated with an increased risk of TN and GR, whereas high TSH levels were associated with thyroid antibody positivity. The research also suggests that adults whose TSH levels at upper or lower limits of the normal range should be reviewed regularly.

Efficacy and Safety in Proton Therapy and Photon Therapy for Patients With Esophageal Cancer: A Meta-Analysis.

Importance: Radiotherapy plays an important role in the treatment of esophageal cancer. Proton therapy has unique physical properties and higher relative biological effectiveness. However, whether proton therapy has greater benefit than photon therapy is still unclear. Objective: To evaluate whether proton was associated with better efficacy and safety outcomes, including dosimetric, prognosis, and toxic effects outcomes, compared with photon therapy and to evaluate the efficacy and safety of proton therapy singly. Data Sources: A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, SinoMed, and China National Knowledge Infrastructure databases was conducted for articles published through November 25, 2021, and updated to March 25, 2023. Study Selection: For the comparison of proton and photon therapy, studies including dosimetric, prognosis, and associated toxic effects outcomes were included. The separate evaluation of proton therapy evaluated the same metrics. Data Extraction and Synthesis: Data on study design, individual characteristics, and outcomes were extracted. If I2 was greater than 50%, the random-effects model was selected. This meta-analysis is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: The main outcomes were organs at risk (OARs) dosimetric outcomes, prognosis (overall survival [OS], progression-free survival [PFS], and objective response rate [ORR]), and radiation-related toxic effects. Results: A total of 45 studies were included in the meta-analysis. For dosimetric analysis, proton therapy was associated with significantly reduced OARs dose. Meta-analysis showed that photon therapy was associated with poor OS (hazard ratio [HR], 1.31; 95% CI, 1.07-1.61; I2 = 11%), but no difference in PFS was observed. Subgroup analysis showed worse OS (HR, 1.42; 95% CI, 1.14-1.78; I2 = 34%) and PFS (HR, 1.48; 95% CI, 1.06-2.08; I2 = 7%) in the radical therapy group with photon therapy. The pathological complete response rate was similar between groups. Proton therapy was associated with significantly decreased grade 2 or higher radiation pneumonitis and pericardial effusion, and grade 4 or higher lymphocytopenia. Single-rate analysis of proton therapy found 89% OS and 65% PFS at 1 year, 71% OS and 56% PFS at 2 years, 63% OS and 48% PFS at 3 years, and 56% OS and 42% PFS at 5 years. The incidence of grade 2 or higher radiation esophagitis was 50%, grade 2 or higher radiation pneumonitis was 2%, grade 2 or higher pleural effusion was 4%, grade 2 or higher pericardial effusion was 3%, grade 3 or higher radiation esophagitis was 8%, and grade 4 or higher lymphocytopenia was 17%. Conclusions and Relevance: In this meta-analysis, proton therapy was associated with reduced OARs doses and toxic effects and improved prognosis compared with photon therapy for esophageal cancer, but caution is warranted. In the future, these findings should be further validated in randomized clinical trials.

Novel mutation of SPG4 gene in a Chinese family with hereditary spastic paraplegia: A case report.

BACKGROUND: Hereditary spastic paraplegia (HSP) is a group of neurogenetic diseases of the corticospinal tract, accompanied by distinct spasticity and weakness of the lower extremities. Mutations in the spastic paraplegia type 4 (SPG4) gene, encoding the spastin protein, are the major cause of the disease. This study reported a Chinese family with HSP caused by a novel mutation of the SPG4 gene. CASE SUMMARY: A 44-year-old male was admitted to our hospital for long-term right lower limb weakness, leg stiffness, and unstable walking. His symptoms gradually worsened, while no obvious muscle atrophy in the lower limbs was found. Neurological examinations revealed that the muscle strength of the lower limbs was normal, and knee reflex hyperreflexia and bilateral positive Babinski signs were detected. Members of his family also had the same symptoms. Using mutation analysis, a novel heterozygous duplication mutation, c.1053dupA, p. (Gln352Thrfs*15), was identified in the SPG4 gene in this family. CONCLUSION: A Chinese family with HSP had a novel mutation of the SPG4 gene, which is autosomal dominant and inherited as pure HSP. The age of onset, sex distribution, and clinical manifestations of all existing living patients in this family were analyzed. The findings may extend the current knowledge on the existing mutations in the SPG4 gene.