Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Objective: To investigate the feasibility and safety of modified interposed jejunal anastomosis following total laparoscopic proximal gastrectomy. Methods: The modification in the digestive tract reconstruction involves transecting the small intestine 2-3 cm below the gastrojejunostomy site and relocating the enteroenterostomy cranially, based on the double-tract anastomosis technique. Specifically, the jejunum and its mesenteric vessels are transected 20-25 cm from the ligament of Treitz. An overlap anastomosis is performed between the esophagus and the distal jejunum, with the common opening closed using a 15 cm barbed suture in a buried manner. A side-to-side gastrojejunostomy is completed under natural anatomical alignment, and the common opening is closed similarly. A side-to-side anastomosis is then created between the small intestine approximately 10 cm below the gastrojejunal anastomosis and the small intestine distal to the ligament of Treitz. Finally, the small intestine is transected 2-3 cm below the gastrojejunal anastomosis without dividing the mesenteric vessels. Results: From April to December 2024, a total of five patients with adenocarcinoma of the esophagogastric junction underwent modified interposed jejunum anastomosis following totally laparoscopic proximal gastrectomy at the Affiliated Tumor Hospital of Xinjiang Medical University. The median age of the group was 56 (53-74) years, including four males and one female, with a median body mass index of 24 (21-29) kg/m². Three cases were classified as Siewert type II and two as type III. All five patients successfully completed the totally laparoscopic proximal gastrectomy with modified interposed jejunum anastomosis. The median operative time was 215 (165-240) minutes, the digestive tract reconstruction time was 75 (65-93) minutes, and the intraoperative blood loss was 50 (30-100) ml. The median time to postoperative flatus was 71 (68-88) hours, with no severe complications occurring in any case. The median postoperative hospital stay was 8 (8-9) days. Within three months after surgery, none of the patients reported reflux symptoms such as acid regurgitation or heartburn. Conclusions: Total laparoscopic modified interposed jejunal anastomosis is safe and feasible, with relatively simple operative steps. It effectively prevents reflux while ensuring the passage of food through the remnant stomach and duodenal loop.
Humans ; Gastrectomy/methods* ; Jejunum/surgery* ; Laparoscopy/methods* ; Anastomosis, Surgical/methods* ; Male ; Female ; Middle Aged ; Aged ; Stomach Neoplasms/surgery* ; Plastic Surgery Procedures/methods*

Several types of soft tissue masses occur in the lower extremities. A mass associated with blood vessels is often difficult to diagnose. A 15-year-old male patient visited the author’s hospital with discomfort and edema in his right calf that had persisted for six months. A physical examination showed no palpable mass other than mild edema. Three masses were found during the ultrasound scan along the small saphenous vein. The masses had a cyst-like appearance and were filled with thrombus. In duplex ultrasound, vascular reflux was represented inside the masses. During surgery, it was suspected that vascular deformation occurred in the small saphenous vein, and simple ligation and resection treatments were performed. The patient was finally diagnosed with venous aneurysms accompanied by thrombosis based on the histology tests. The symptoms disappeared after surgery, and there were no recurrences or unusual findings at the follow-up one year later. Venous aneurysms occurring in the superficial veins of the lower extremities are rarely reported, but treatment and diagnosis are important. This paper reports a case of an aneurysm on the small saphenous vein.

Intracranial arterial disease (ICAD) is a heterogeneous condition characterized by distinct pathologies, including atherosclerosis. Advances in magnetic resonance technology have enabled the visualization of intracranial arteries using high-resolution vessel wall imaging (HR-VWI). This review summarizes the anatomical, embryological, and histological differences between the intracranial and extracranial arteries. Next, we review the heterogeneous pathophysiology of ICAD, including atherosclerosis, moyamoya or RNF213 spectrum disease, intracranial dissection, and vasculitis. We also discuss how advances in HR-VWI can be used to differentiate ICAD etiologies. We emphasize that one should consider clinical presentation and timing of imaging in the absence of pathology-radiology correlation data. Future research should focus on understanding the temporal profile of HR-VWI findings and developing quantitative interpretative approaches to improve the decision-making and management of ICAD.

Background: and Purpose Nelonemdaz (Neu2000) has both selective antagonism against 2B subunit of N-methyl-D-aspartate receptor and antioxidant activity. This drug provides sufficient evidence of neuroprotection in acute cerebral ischemia/reperfusion models. This phase III trial aims to determine this effect in patients.Design The Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz is a multicenter, double-blinded clinical trial. A total of 496 patients will be randomly assigned into the nelonemdaz (a total of 5,250 mg divided by 10 times for 5 days) and placebo groups. Patients will be included if they have an acute ischemic stroke (National Institutes of Health Stroke Scale score ≥8) caused by intracranial large vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score ≥4), and if they are expected to undergo endovascular thrombectomy within 12 hours after stroke onset.Endpoints The primary endpoint is a favorable shift in the modified Rankin Scale (mRS) score at 90 days after the first dose of drug. The data will be analyzed by the Cochran–Mantel–Haenszel shift test. The secondary endpoints include functional independence (mRS 0–2) at 35 and 90 days, the favorable shift of mRS at 35 days, the proportion of mRS 0 at 35 and 90 days, and the occurrence rates of symptomatic intracranial hemorrhage within 7 days. Conclusion This trial will clarify the efficacy and safety of nelonemdaz in patients with acute ischemic stroke and endovascular thrombectomy. This study has been registered at ClinicalTrials. gov (NCT05041010).