Objective To compare the long-term survival of elderly patients with esophageal squamous cell carcinoma (ESCC) treated with surgical versus non-surgical treatment. Methods A retrospective analysis was conducted on the clinical data of elderly patients aged ≥70 years with ESCC who underwent esophagectomy or radiotherapy/chemotherapy at Sichuan Cancer Hospital from January 2009 to September 2017. Patients were divided into a surgical group (S group) and a non-surgical group (NS group) according to the treatment method. The propensity score matching method was used to match the two groups of patients at a ratio of 1∶1, and the survival of the two groups before and after matching was analyzed. Results A total of 726 elderly patients with ESCC were included, including 552 males and 174 females, with 651 patients aged ≥70-80 years and 75 patients aged ≥80-90 years. There were 515 patients in the S group and 211 patients in the NS group. The median follow-up time was 60.8 months, and the median overall survival of the S group was 41.9 months [95%CI (35.2, 48.5)], while that of the NS group was only 24.0 months [95%CI (19.8, 28.3)]. The 1-, 3-, and 5-year overall survival rates of the S group were 84%, 54%, and 40%, respectively, while those of the NS group were 72%, 40%, and 30%, respectively [HR=0.689, 95%CI (0.559, 0.849), P<0.001]. After matching, 138 patients were included in each group, and there was no statistical difference in the overall survival between the two groups [HR=0.871, 95%CI (0.649, 1.167), P=0.352]. Conclusion Compared with conservative treatment, there is no significant difference in the long-term survival of elderly patients aged ≥70 years who undergo esophagectomy for ESCC. Neoadjuvant therapy combined with surgery is still an important choice to potentially improve the survival of elderly patients with ESCC.

ObjectiveTo observe the effects of the South African herb Hoodia gordonii （HG） on glucolipid metabolism in diabetic db/db mice and explore the possible mechanisms of HG on the liver of db/db mice based on the phosphoinositide-3 kinase （PI3K）/protein kinase B （Akt）/factor forkhead protein O1 （FoxO1） signaling pathway. MethodA total of 30 db/db mice were randomly divided into five groups according to fasting blood glucose： model group， metformin group （0.195 g·kg^-1）， and low dose （0.39 g·kg^-1）， medium dose （0.78 g·kg^-1）， and high dose （1.56 g·kg^-1） HG groups， with six m/m mice in each group， and another six m/m mice were set as normal group. The mice in the normal and model groups were given saline of 9 mL·kg^-1 by gavage. Body weight， water intake， and fasting blood glucose of the mice in each group were measured weekly. After six weeks of continuous administration， serum insulin （FINS）， low-density lipoprotein cholesterol （LDL）， total cholesterol （TC）， triglyceride （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， urea， and creatinine （CREA） were measured， and liver sections were embedded and stained with hematoxylin-eosin （HE）， periodic acid-Schiff （PAS）， and oil red O. Protein expression of PI3K p85， p-Akt， and p-FoxO1 in liver was detected by immunohistochemistry. The mRNA expression of PI3K， Akt， and FoxO1 in liver tissue was detected by real-time polymerase chain reaction （Real-time PCR）. ResultAfter six weeks of administration intervention， it was found that fasting blood glucose was significantly downregulated in mice in the three HG groups （P<0.05）. The level of islet resistance index was significantly reduced in both the low and medium dose HG groups （P<0.05）. The expression levels of TC， TG， and LDL were reduced in all HG groups （P<0.05， P<0.01）. Pathologically， HG could alleviate hepatocyte steatosis， reduce the volume and content of lipid droplets in liver， and increase the distribution of glycogen granules in liver to some extent in mice. Immunohistochemical assays revealed that PI3K p85 protein expression was significantly increased in the low， medium， and high dose HG groups compared with the model group （P<0.01）. p-Akt protein expression was significantly increased in the medium and high dose HG groups （P<0.05， P<0.01）. p-FoxO1 protein expression was significantly increased in the low， medium， and high dose HG groups （P<0.05， P<0.01）. Compared with the model group， PI3K mRNA was increased in low dose， medium dose， and high dose HG groups （P<0.05）， and Akt mRNA was increased in high dose HG group （P<0.05）. FoxO1 mRNA was decreased in low dose， medium dose， and high dose HG groups （P<0.05）. ConclusionHG can ameliorate the disorder of glucolipid metabolism in db/db mice， which may be related to its activation of the hepatic PI3K/Akt/FoxO1 signaling pathway.

BACKGROUND:Ischemic stroke is a serious threat to human health.After ischemia and hypoxia,astrocyte expresses lipocalin-2 in large amounts to aggravate brain injury,but the specific mechanism is not clear.Hydroxysafflor yellow A has anti-ischemia,anti-oxidation,anti-thrombosis and anti-inflammatory effects.However,whether hydroxysafflor yellow A affects the expression of lipocalin-2 in astrocytes after cerebral ischemia and hypoxia and its mechanism are not clear. OBJECTIVE:To investigate the effect and mechanism of hydroxysafflor yellow A on the expression of lipocalin-2 in astrocytes after cerebral ischemia and reperfusion. METHODS:(1)Thirty adult SD rats were randomly divided into three groups:sham operation group,middle cerebral artery occlusion and reperfusion group,and hydroxysafflor yellow A group.The middle cerebral artery occlusion and reperfusion model was established in the latter two groups,and hydroxysafflor yellow A group was intraperitoneally injected with 12 mg/kg hydroxysafflor yellow A after reperfusion.Longa score was used to evaluate the degree of neurological impairment.Infarct volume was determined by TTC staining.JAK2/STAT3 pathway and lipocalin-2 expression were detected by western blot assay and immunofluorescence.Levels of interleukin 1β,interleukin 6 and tumor necrosis factor α were detected by ELISA.(2)Astrocytes were divided into four groups:Normal group,glucose-oxygen deprivation group,hydroxysafflor yellow A group and AG490 group.In the latter three groups,glucose-oxygen deprivation and glucose-oxygen recovery models were established.Astrocytes were treated with 75 μmol/L hydroxysafflor yellow A and 10 μmol/L tyrosine phosphorylation inhibitor AG490 for 8 hours during glucose-oxygen deprivation,respectively.The mechanism of hydroxysafflor yellow A on lipocalin-2 was further verified. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,cerebral infarction was significantly increased in the middle cerebral artery occlusion and reperfusion group,accompanied by aggravated neurological impairment(P<0.01).Hydroxysafflor yellow A treatment could reduce cerebral infarction volume and improve neurological function(P<0.01).(2)The expressions of p-JAK2,p-STAT3 and lipocalin-2 in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A treatment reduced the expressions of JAK2,STAT3 and lipocalin-2(P<0.01).(3)The expression levels of interleukin 1β,interleukin-6 and tumor necrosis factor α in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A inhibited the expressions of interleukin 1β,interleukin-6 and tumor necrosis factor α(P<0.01).(4)In vitro,the expressions of p-JAK2,p-STAT3 and lipocalin-2 in the glucose-oxygen deprivation group were significantly higher than those in the normal group(P<0.01).After adding AG490,the phosphorylation of JAK2 and STAT3 decreased,and the expression of lipocalin-2 was inhibited(P<0.01).The results suggest that hydroxysafflor yellow A may inhibit the expression of lipocalin-2 in astrocytes after ischemia and hypoxia by regulating the JAK2/STAT3 signaling pathway,thereby reducing brain injury.

Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.

Tumor-associated macrophages(TAMs)are the predominant cell group in the tumor microenvironment(TME)and are the most important regulatory cells of immune system suppression and tumor cell proliferation in TIME.Src homology-2 domain-containing protein tyrosine phosphatase 2(SHP-2)is a non-receptor protein tyrosine phosphatase that plays an important role in the transmission of signals from the cell surface to the nucleus.SHP-2 is a key intracellular regulatory factor mediating cell proliferation and differentiation and is involved in a variety of growth factor and cytokine signaling pathways linking the cell surface to the nucleus.Recent studies have shown that SHP-2 is a key enzyme in determining the function of TAMs,but because of its variable function,it plays different or even opposite roles in different solid TMEs.This paper reviews the function of SHP-2 in TAMs and related solid tumors to provide a comprehensive reference for tumor immunity and targeted therapy research.

Objective:To evaluate the clinical application value of the adaptive aperture by comparing intensity-modulated proton radiotherapy(IMPT) plans using and not using the aperture for brain tumors.Methods:A total of twenty patients treated with postoperative radiotherapy for brain tumors were enrolled in this study. IMPT plans were developed for each patient using and not using the adaptive aperture under the same optimization conditions. The target conformal index (CI) value, target homogeneity index (HI) value, and the dose to normal tissues of the two sets of plans were compared.Results:The IMPT plans designed using the adaptive aperture significantly increased the mean CI value from 0.58 to 0.66, while decreasing the mean 50% prescription dose volume from 797.70 cm 3 to 638.15 cm 3. These plans also reduced the irradiation doses to the cochlea, brainstem, optic chiasm, optic nerve, and lens ( t = 2.06, 3.02, 2.11, 2.58, 2.67, P < 0.05). Additionally, there was no significant difference in the HI value of the target volumes and the machine jumps (MU) between the two sets of plans ( P > 0.05). Conclusions:The adaptive aperture can significantly reduce the irradiation dose to normal tissues outside the target volumes, positively impacting the protection of organs at risk (OARs) around the target values. This demonstrates its great potential for clinical application.

Objective:To investigate the clinicopathological characteristics of early gastric cancer with mixed histological staging, and to analyze the prognostic effect of endoscopic submucosal dissection (ESD) for early gastric cancer.Methods:Clinical data of early gastric cancer patients treated with ESD in Gansu Wuwei Cancer Hospital from January 2011 to March 2020 were collected, and clinicopathological characteristics of patients with mixed-type early gastric cancer were analyzed by descriptive statistical methods. The clinical effects and influencing factors of ESD on early gastric cancer were analyzed by logistic regression. Kaplan-Meier was used to estimate the survival rate, and log-rank test was used to compare the survival rate.Results:A total of 269 patients (280 lesions) were included in this study, including 216 males (80.30%) and 53 females (19.70%), with age of 60.43±8.01 years. There were 25 lesions (8.93%) of mixed early gastric cancer, 248 lesions (88.57%) of differentiated early gastric cancer, and 7 lesions (2.50%) of undifferentiated early gastric cancer. Compared with differentiated and undifferentiated early gastric cancer, the lesion site of mixed early gastric cancer was mainly located in the upper 1/3 of the stomach [64.00% (16/25), 40.73% (101/248) VS 0.00% (0/7), χ2=10.211, P=0.006], the proportion of the lesion size ≤2 cm was relatively small [52.00% (13/25), 80.65% (200/248) VS 85.71% (6/7), χ2=11.173, P=0.004], and the proportion of infiltration depth in the mucosa was lower [52.00% (13/25), 85.48% (212/248) VS 57.14% (4/7), χ2=20.019, P<0.001], the proportion of positive vertical resection margin was relatively high [20.00% (5/25), 2.82% (7/248) VS 0.00% (0/7), χ2=16.657, P<0.001], the proportion of vascular invasion was higher than that of differentiated carcinoma but lower than that of undifferentiated carcinoma [36.00% (9/25), 2.42% (6/248) VS 42.86% (3/7), χ2=58.413, P<0.001], the complete resection rate was lower [76.00% (19/25), 93.15% (231/248) VS 100.00% (7/7), χ2=9.497, P=0.009], the curative resection rate was lower than that of differentiated early gastric cancer, but higher than that of undifferentiated early gastric cancer [48.00% (12/25), 89.52% (222/248) VS 42.86% (3/7), χ2=39.757, P<0.001], and the proportion of eCura grade C2 was higher than that of differentiated cancer, but lower than that of undifferentiated cancer [48.00% (12/25), 5.65% (14/248) VS 57.14% (4/7), χ2=58.766, P<0.001]. The results of multivariate analysis showed that the larger lesions ( P=0.004, OR=0.539, 95% CI: 0.354-0.822) was the risk factor for curative resection. In terms of infiltration depth, mucosal ( P=0.001, OR=51.799, 95% CI: 5.535-84.768) and submucosal 1 ( P<0.001, OR=29.301, 95% CI: 24.694-73.972) were protective factors for curative resection compared with submucosal 2. In terms of differentiation degree, compared with mixed type, differentiated type ( P=0.024, OR=3.947, 95% CI: 1.195-13.032) was the protective factor for curative resection, while undifferentiated type ( P=0.443, OR=0.424, 95% CI: 0.048-3.788) showed no difference between curative resection and mixed type. During the follow-up, 7 patients died. The overall survival time was 114.42±0.97 months, and the 5-year survival rate was 97.10%. There was no significant difference in the survival rate of early gastric cancer patients with different degrees of differentiation ( χ2=0.434, P=0.805). The survival rate of early gastric cancer patients with or without curative resection was significantly different ( χ2=4.081, P=0.043). Conclusion:Mixed early gastric cancer patients show high margin positive rate, vascular infiltration, and less curative resection than differentiated early gastric cancer. Therefore, the process of treating mixed early gastric cancer should be more rigorous. The long-term survival prognosis of early gastric cancer after ESD treatment is promising.

Objective To present and discuss beam characteristics of the first Mevion S250i gantry-mounted accelerator pencil beam scanning proton therapy system in China.Methods The output dose was measured using a parallel-plate ionization chamber.The integrated depth dose was measured with a large-radius Bragg peak ionization chamber,covering 19 energy levels ranging from 227 MeV to 28 MeV,to analyze the proton beam characteristics.The spots in the air were measured with Phoenix flat panel detector on the beam central axis,and the precision of the delivery position was verified by measuring the multi-spot beam map.The interleaf leakage and penumbra reduction of adaptive aperture were measured to characterize its performance.Results The proton system was calibrated for a maximum energy of 227 MeV,with a(10×10)cm2uniform field delivering 1 Gy dose at a depth of 5 cm underwater.The system effectively modulated the proton beam range to the patient's surface,maintaining a constant 80%-80%Bragg peak width of 8.6 mm at all energy levels.The spot size of the highest energy beam at the isocenter was about 4 mm in the air,and the spot delivery position error was less than 1 mm.The interleaf leakage rate of the adaptive aperture for the highest energy beam was below 1.5%,and the penumbra was significantly reduced.Conclusion Mevion S250i proton therapy system demonstrates unique design and beam characteristics,which is reflected in the Bragg peak shape,spot size variation with energy,and penumbra sharpening of adaptive aperture;and these differences should be considered in treatment planning system modeling and planning for precision treatment.

Objective To investigate the therapeutic effectiveness of ozone combined with low-temperature plasma coagulation therapy on patients with cervical spondylotic radiculopathy and its influence on inflammatory responses.Methods Ozone in combination with low-temperature plasma radio-frequency coagulation was applied to 75 patients with cervical spondylotic radiculopathy in Pain Medicine Department of Capital Medical University Affiliated Beijing Anzhen Hospital from May 2022 to May 2023.Pain scores were assessed using Visual Analog Scale(VAS)and Neck Disability Index(NDI)before and two weeks after treatment.Enzyme-linked immunosor-bent assay(ELISA)was used to analyze the level of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6)and interferon-gamma(IFN-γ)before and two weeks after treatment.Results After treatment with ozone plus low-temperature plasma radiofrequency,VAS and NDI scores showed a significant decrease[VAS:5.36(4,7)vs.1.32(1,2),P＜0.000 1;NDI:32.72(24,70)vs.7.62(3.55,8.9),P＜0.000 1].Two weeks after surgical intervention,there was an effective reduction in the level of IL-6,TNF-αand IFN-γ alleviating the inflammatory re-sponse[IL-6:4.33(2.51,5.04)vs.3.49(2.08,4.43),P＜0.05;TNF-α:1.95(1.41,2.21)vs.1.61(1.02,2.03),P＜0.05;IFN-γ:1.84(1.18,2.47)vs.1.55(0.76,2.09),P＜0.05].Conclusions This Ozone combined with low-temperature plasma radiofrequency ablation is an effective technology for treatment of cer-vical spondylotic radiculopathy.

Objective:To discuss the acceptance test of beam performance and mechanical precision of the first Mevion type S250i proton therapy system in China,and verify the stability and reliability of that in clinical treatment.Methods:According to the requirements of acceptance report of manufacturer,the output and range of machine unit(MU),the accuracy and stability of size and position of beam spot,the penumbra and position accuracy of adaptive aperture(AA)of Mevion type S250i proton therapy system,as well as the tests of mechanical properties and functions of the requirement of clinical use,were checked and tested for acceptance.Results:The maximum deviation of MU output was 1.3%,and the maximum deviation of the range was 0.037 g/cm2,and the maximum distal fall-off was 0.465 cm,and the minimum range of energy modulation was 0.21 g/cm2.The maximum deviations of the size of beam spot and the maximum deviation of the position were respectively 0.07 cm and 0.05 cm.The maximum AA penumbra was 0.007 cm,and the AA position accuracy was less than 0.1 cm.Conclusion:The acceptance test of the Mevion type S250i proton therapy system indicates that the parameters of the beam performance and mechanical precision can meet the requirements of the acceptance contract and AAPM-TG224 report of manufacturer,which has verified the machine has better favorable stability and reliability.