Cholesterol,as an important component of cell membranes,plays a multifaceted role in mediating tumor immunomodulation and drug intervention.In case of cholesterol metabolic imbalance,the accumulation of cholesterol metabolic intermediates,the changes in concentrations,and the regulation of related signaling pathways can affect tumor immunity by promoting inflammation and inhibiting immune cell function.Preclinical and clinical studies have shown that controlling cholesterol metabolism can inhibit tumor growth,re-shape body immune regulation,and enhance antitumor immunity.A deep understanding of the association between immune cells and cholesterol metabolic pathways in the tumor microenvironment can help to develop novel drugs targeting cholesterol metabolism.This article reviews the multifaceted role of cholesterol and its derived metabolites in the tumor microenvironment by regulating various types of immune cells such as myeloid-derived suppressor cells,tumor-associated macrophages,dendritic cells,and T-lymphocytes,as well as the characteristics of tumor immunomodulation mediated by cholesterol metabolism and the advances in pharmaceutical re-search on improving the immune function of the body by intervening against cholesterol,in order to further provide new ideas and a thera-peutic basis for cholesterol modulation and intervention in tumor im-munotherapy.

Objective To experimentally validate the effects of a self-developed heat-stable thickening agent on the textual characteristics of enteral nutrition solutions of standard concentration and its applicability in improving dysphagia.Methods A gradient of different doses of the self-developed thickening agent(1.0 g,1.5 g,2.0 g,2.5 g,and 3.0 g)and three commonly used commercial thickeners were mixed with 23.391 g of a complete nutrition formula powder dissolved in 85 mL of purified water to prepare 100 mL standard concentration nutrition solutions.The textual parameters(cohesiveness,viscosity,thickness,and hardness)of these nutrition solutions were measured using a texture analyzer at various temperature gradients(20℃,40℃,60℃,and 80℃)to compare their thermal stability.A dysphagia rat model was created via epiglottectomy to explore the effects of the thickener on lung tissue damage scores and levels of inflammatory markers.The rats were divided into a test intervention group,a positive control group,a negative control group,and a blank control group(no surgery and normal feeding after fasting for one day),with 15 rats in each group.After fasting for one day post-surgery,the test intervention group was fed with the standard concentration nutrition solution thickened with the self-developed thickener,while the positive control group was given a standard concentration nutrition solution thickened with product 3,and the negative control group was fed a normal diet.All groups were fed for two weeks with food dyed with food-grade green dye.General conditions,body mass,and food intake were observed and recorded.After two weeks,abdominal aorta blood was collected,and heart,liver,spleen,lung,and kidney tissues were harvested and weighed to calculate the lung tissue organ coefficient.The organ conditions were evaluated using routine H&E staining,and lung damage was semi-quantitatively analyzed based on the Mikawa scoring criteria.Blood supernatants were collected to measure the total serum protein and albumin levels to determine the nutritional status of the rats.The expression of IL-6 and TNF-α genes in lung tissues was measured by RT-qPCR.IL-6 and TNF-α protein expression levels in lung tissues,lung tissue homogenate,and serum were measured by ELISA.The aspiration incidence rate was calculated.Results Within the dosage range of 1.0 g to 3.0 g,the self-developed thickener in the test samples exhibited superior thermal stability in cohesiveness compared to the three commercially available thickeners,with a statistically significant difference(P<0.01).The differences in the thermal stability of viscosity and hardness between the self-developed thickener and the three commercially available thickeners were not statistically significant.The viscosity stability was optimal for the self-developed thickener,followed by the commercially available thickeners 1 and 3,with thickeners 2 being the least stable,though the differences were not statistically significant(P>0.05).Product 1 showed the best thermal stability in thickness,followed by the self-developed thickener and product 2,while the product 3 exhibited the worst performance,with the difference being statistically significant(P<0.01).The self-developed thickener had the best thermal stability in hardness at temperatures ranging from 20℃to 80℃,followed by products 1 and 2,with product 3 being the least stable.However,the differences were not statistically significant(P>0.05).Animal experiment results indicated that the body weight gain in the positive control group and the test intervention group was lower than that in the blank and negative control groups(P<0.01).The spleen coefficient of the intervention group was lower than that of the positive control group and the blank control group(P<0.01),while the heart,liver,and kidney coefficients were lower than those of the blank control group(P<0.01).The differences in the lung coefficient of the intervention group and those of the other three groups were no statistically significant.Levels of TP and ALB in the test intervention group,the positive control group,and the negative control group were all lower than those in the blank control group,with statistically significant differences(P<0.01).ELISA results showed that serum IL-6 levels in the blank and test intervention groups were lower than those in the negative and positive control groups(P<0.05),while the difference in the other indicators across the four groups were not statistically significant(P>0.05).There were no statistically significant differences among the four groups in terms of lung tissue damage pathology scores,or in the levels of IL-6 and TNF-α gene expression in lung tissues.The aspiration incidence rate was 0% in all groups.Conclusion The self-developed enteral nutrition thickening agent demonstrated excellent thermal stability and swallowing safety.Further research to explore its application in patients with dysphagia is warranted.

Objective To observe the effect of Xiaochaihutang on ammonia-induced edema of astrocytes in rats and explore the mechanism of Xiaochaihutang in the treatment of cerebral edema based on NF-κB signaling pathway.Methods Astrocytes were isolated from the cerebral cortex of SD rats 1-2 days old.When the cell content was more than 95%,the cells could be subcultured and divided into three groups:Vehicle group(10%blank control group serum,Vehicle),Model group(10%blank control group serum+5 mmol·L-1 ammonium chloride,Model),and Xiaochaihutang group(10%serum+5 mmol·L-1 ammonium chloride,XCHT).The expression of AQP4 was detected by immunofluorescence.The levels of AQP4,GFAP,and TNF-α were detected by RT-PCR and Western blot.NF-κB P65 was measured by Western blot.Results ① Ammonium chloride increased the expression of AQP4 in astrocytes(P<0.01)and decreased the expression of GFAP(P<0.05,P<0.01),however,the expression of AQP4 in astrocytes decreased(P<0.01)while GFAP increased(P<0.05)after the intervention of serum containing Xiaochaihutang.② Compared with the Vehicle group,the expression level of TNF-α and phosphorylation of NF-κB P65 in the Model group was significantly increased(P<0.05),while after Xiaochaihutang serum medicated treatment,TNF-α and phosphorylation of NF-κB P65 content lower(P<0.05).Conclusion Xiaochaihutang can improve the edema of astrocytes induced by ammonia and enhance the activity of astrocytes.Its mechanism may be related to inhibition of NF-κB signaling pathways,and reduce inflammation medium(especially TNF-α)produced and released.

Objective:To analyze the clinical effects of the pre-expanded internal mammary artery perforator flap in large chest keloids surgical treatment.Methods:Patients with large chest keloid were treated with the pre-expanded internal mammary artery perforator flap between January 2017 and September 2021. The surgical treatment was divided into two different phases. In the first phase, a tissue expander was implanted beneath the skin within the angiosome of the internal mammary artery perforator. The expander was injected with normal saline once a week. In the second phase, the expander and the keloid tissue were removed, and a pre-expanded internal mammary artery perforator flap was designed to cover the wound. Radiotherapy and hyperbaric oxygen therapy were performed in the postoperative period. The treatment effect was followed up. The postoperative complications were analyzed, and the recurrence and patient satisfaction rates were recorded.Results:A total of 41 patients were enrolled, including 20 male and 21 female patients. The patients’ age ranged from 24 to 64, with a mean disease history of 11.9 years. The mean size of the keloid was 9 cm × 8 cm. Some patients were treated with one expander, but four expanders were needed in some extensive cases. The volume of the expander ranged from 80 to 600 ml. The mean volume was 300 ml, with a mean expansion time of 3 months. The mean flap size was 9 cm × 8 cm. Two cases with distal necrosis were observed. Five cases suffered from partial incision scar hyperplasia. No recurrence occurred during the followed-up period. Thirty-six patients (87.8%) were satisfied with the operation effect, and five (12.2%) thought the effect was acceptable.Conclusions:The pre-expanded internal mammary artery perforator flap is an effective treatment for the large chest keloid. It can provide sufficient skin tissue for wound repair, with a stable blood supply and an excellent curative effect.

Objective:To analyze the clinical effects of the pre-expanded internal mammary artery perforator flap in large chest keloids surgical treatment.Methods:Patients with large chest keloid were treated with the pre-expanded internal mammary artery perforator flap between January 2017 and September 2021. The surgical treatment was divided into two different phases. In the first phase, a tissue expander was implanted beneath the skin within the angiosome of the internal mammary artery perforator. The expander was injected with normal saline once a week. In the second phase, the expander and the keloid tissue were removed, and a pre-expanded internal mammary artery perforator flap was designed to cover the wound. Radiotherapy and hyperbaric oxygen therapy were performed in the postoperative period. The treatment effect was followed up. The postoperative complications were analyzed, and the recurrence and patient satisfaction rates were recorded.Results:A total of 41 patients were enrolled, including 20 male and 21 female patients. The patients’ age ranged from 24 to 64, with a mean disease history of 11.9 years. The mean size of the keloid was 9 cm × 8 cm. Some patients were treated with one expander, but four expanders were needed in some extensive cases. The volume of the expander ranged from 80 to 600 ml. The mean volume was 300 ml, with a mean expansion time of 3 months. The mean flap size was 9 cm × 8 cm. Two cases with distal necrosis were observed. Five cases suffered from partial incision scar hyperplasia. No recurrence occurred during the followed-up period. Thirty-six patients (87.8%) were satisfied with the operation effect, and five (12.2%) thought the effect was acceptable.Conclusions:The pre-expanded internal mammary artery perforator flap is an effective treatment for the large chest keloid. It can provide sufficient skin tissue for wound repair, with a stable blood supply and an excellent curative effect.

Objective:To evaluate the influence of optimized rehabilitation process on prognosis of old patients with Evans type III and IV femoral intertrochanteric fractures and investigate the related efficacy.Methods:A retrospective case-control study was performed on 207 old patients with Evans type III and IV femoral intertrochanteric fractures fixed by proximal femoral nail anti-rotation (PFNA Ⅱ) in People's Hospital of Chongqing Banan District from March 2012 to January 2017. Normal rehabilitation group ( n=100) had rehabilitation education and training after operation and started off-bed exercise at postoperative 48 hours, including 38 males and 62 females, with age from 65 to 75 years in 69 patients and 75 years and over in 31 patients. There were 49 patients with Evans type III fractures and 51 with Evans IV fractures. Optimized rehabilitation group ( n=107) had rehabilitation education and training at admission and started off-bed exercise within 48 hours after operation, including 43 males and 64 females, with age from 65 to 75 years in 79 patients and 75 years and over in 28 patients. There were 63 patients with Evans III fractures and 44 with Evans IV fractures. Operation time, intraoperative bleeding, complications during hospital stay, fracture healing time, internal fixation rupture, femoral head cut, second fracture and mortality rate were recorded and compared between the two groups. Harris hip score was evaluated at postoperative 3, 6 and 12 months. Results:All patients were followed up for 3-12 months, with the average of 11.6 months. Normal rehabilitation group showed introperative bleeding of (119.3±1.9)ml and operation time of (1.13±0.22)hours, which were not significantly differed from that in optimized rehabilitation group [( 121.6±1.2)ml, (1.07±0.25)h] ( P>0.05). In normal rehabilitation group, the complications were hypostatic pneumonia in 19 patients, heart failure or acute myocardial infarction in 8, urinary infection in 18, lower-extremity deep vein thrombosis in 5, pressure ulcer in 4, with 5 deaths within 3 months after surgery. While in optimized rehabilitation group, the complications during hospitalization were hypostatic pneumonia in 6 patients, urinary infection in 6, heart failure or acute myocardial infarction in 1, lower-extremity deep vein thrombosis in 1, pressure ulcer in 0 during hospital ( P<0.05). Within 3 months, mortality rate was 5% in normal rehabilitation group compared to zero in optimized rehabilitation group ( P<0.05). At postoperative 3 months, 6 months and 12 months, Harris hip scores in optimized rehabilitation group[(69.7±6.3)points, (80.2±4.6)points, (89.3±10.2)points] were significantly higher than that in normal rehabilitation group [(53.6±5.4)points, (75.1±9.2)points, (77.5±7.5)points]( P<0.05). Fracture healing time, internal fixation rupture, femoral head cut, second fracture and mortality rate at postoperative 12 months had no significant differences between the two groups ( P>0.05). Conclusion:Optimized rehabilitation process can improve hip function, reduce complication rate and mortality rate at postoperative 3 months in old patients with Evans type III and IV femoral intertrochanteric fractures, which deserves clinical application.

Objective: To evaluate the safety and efficacy of helical tomotherapy using simultaneously integrated boost and simultaneous integrated protection technique in the treatment of unresectable biliary tract cancers. Methods: The data of 23 patients with unresectable biliary tract cancer who received tomotherapy-based hypofractionated radiotherapy at Comprehensive Cancer Centre of Drum Tower Hospital,the Affiliated Drum Tower Clinical College of Nanjing Medical University between February 2015 and October 2017 were analyzed. There were 10 males and 13 females, aged from 40 to 85 years(median:58 years). Pathological type included intrahepatic cholangiocarcinomas(n=11), gallbladder cancers(n=6),extrahepatic cholangiocarcinomas(n=6). The irradiated sites covered primary tumors and areas of local invasion,including metastatic lymph nodes which were confined to the abdominal or retroperitoneal space. Dose escalation was achieved using simultaneously integrated boost(SIB) technique, and simultaneous integrated protection(SIP)technique was used to protect gastrointestinal tracts and other adjacent organs. Cox regression modal and Kaplan-Meier analysis were used to analyze the associations between patients′ characteristics and overall survival(OS). Results: The median total radiation dose was 54 Gy(range: 28-72 Gy)and median biologically effective dose(BED)was 74.4 Gy(range: 37.8-115.2 Gy).The median planning target volume(PTV)was 445.79 cm³(range:126.02-950.12 cm³). Based on the various PTV,patients received 2.4-6.0 Gy/fraction with 8-28 fractions. The local control rate was 65.2% and the median OS was 11.3 months(range:2.1-31.9 months).The most common cause of death was out-field failure and only 3 patients died of in-field failures. The longest survival was 31.9 months. BED≥70 Gy significantly improved OS,compared to BED<70 Gy(16.8 months vs.5.1 months)(HR=0.146, 95%CI:0.028-0.762, P=0.022). No patients developed grade ≥4 toxicities. Conclusions Helical tomotherapy-based hypofractionated radiotherapy is effective and well tolerated for patients with unresectable biliary tract cancer. The dose escalation with higher BED could improve the survival for such patients.

Objective To investigate the clinical,imaging,intestinal pathological characteristics and prognosis of gluten ataxia (GA).Methods The clinical data,treatment and prognosis in a patient with GA that was confirmed by pathology and hospitalized in the Department of Neurology,China-Japan Friendship Hospital in July 2018,were analyzed retrospectively.The related literature was reviewed and the clinical feature was summarized.Results The patient is a 41-year old man.He suffered from progressive cerebellar ataxia,and the brain magnetic resonance imaging exhibited diffused cerebellar atrophy.Serum human leukocyte antigen (HLA) tests showed that the patient carried HLA-DQ2 genotype.IgA type anti-gliadin antibody was positive (39.39 RU/ml).Duodenoscopy biopsy revealed mild villus atrophy and lymphocytic infiltration,indicating celiac disease.The diagnosis of GA was established then and the patient was administered gluten-free diet combined with intravenous immunoglobulin,which markedly improved the cerebellar symptoms and signs of cerebellar speech,walk capability and daily living activities.He could do long distance driving independently two months later.Conclusions GA is one of immune-mediated reversible acquired cerebellar ataxia caused by gluten sensitivity.The genotype,serologic features,and clinical phenotype of GA in Chinese mainland population might be similar with those in European and American countries.

Objective To investigate the clinical manifestations, genetic basis and related literatures of Boucher-Neuh(a)user syndrome(BNS), hoping to help physicians recognize this rare disease. Methods A 25-year-old BNS patient was reported.The clinical manifestations and the laboratory data including fundus examination, blood testing, brain MRI and genetic data were summarized.The related literatures were also reviewed.Results The patient presented with tremors, ataxia, secondary sexual characteristics dysplasia,epilepsy, and then got worse progressively.Brain MRI showed severe cerebellar atrophy.Two mutations of PNPLA6 gene were found: one is the heterozygous mutation c.1811C >T (p.A604V),which has not been reported;another is c.2990C>T(p.S997L),which has been reported as a pathogenic mutation related to BNS.Conclusion PNPLA6-related BNS may be considered for adolescent patients with tremor and ataxia,secondary sexual characteristics dysplasia and epilepsy.

Objective: To investigate the expression of miR-212 and miR-132 in the serum of patients with primary liver cancer and their targeted regulation of GP73. Methods: The patients with liver cancer, chronic hepatitis B, or liver cirrhosis who were hospitalized in Taizhou People’s Hospital from January 2015 to December 2016 were enrolled, and healthy volunteers were also enrolled as controls. Quantitative real-time PCR was used to measure the serum levels of miR-212 and miR-132, and the association between the expression of serum miR-212 and miR-132 and the clinicopathological features of patients with liver cancer was analyzed. A Spearman’s rank correlation analysis was used to analyze the correlation between serum miR-212/miR-132 and GP73. Western blot was used to measure the protein expression of GP73, and MTT assay was used to measure the survival rate of cells. The Levene’s homogeneity of variance test was used for data analysis. The independent samples t-test was used for comparison of means between two samples, and ANOVA was used for comparison of means between multiple samples. Results: A total of 90 patients with liver cancer, 60 with chronic hepatitis B, 68 with liver cirrhosis, and 100 healthy volunteers were enrolled. The relative expression levels of miR-212 and miR-132 in serum were 0.046 6 ± 0.024 7 and 0.005 9 ± 0.003 0 in the patients with liver cancer, 0.979 7 ± 0.259 5 and 1.001 8 ± 0.249 9 in the healthy volunteers, 0.588 2 ± 0.216 5 and 0.345 7 ± 0.233 8 in the patients with hepatitis, and 0.313 8 ± 0.153 3 and 0.080 1 ± 0.042 66 in the patients with liver cirrhosis. Compared with the normal controls, all patients had significant reductions in the expression of serum miR-212 (t = 10.26, 20.86, and 35.80, all P < 0.01) and miR-132 (t = 16.55, 36.09, and 39.85, all P < 0.01). In the patients with liver cancer, the relative expression of miR-212 and miR-132 was negatively correlated with alpha-fetoprotein (miR-212: t = -4.46, P < 0.01; miR-132: t = -4.83, P < 0.01), TNM stage (miR-212: t = 6.569, P < 0.01; miR-132: t = 7.31, P < 0.01), degree of tumor differentiation (miR-212: t = 5.268, P < 0.01; miR-132: t = 5.914, P < 0.01), and presence of portal vein tumor thrombus (miR-212: t = 5.16, P < 0.01; miR-132: t = 3.681, P < 0.01), while it was not correlated with tumor size (miR-212: t = 0.687, P > 0.05; miR-132: t = 0.887, P > 0.05). In addition, serum miR-212 and miR-132 were negatively correlated with GP73 in the patients with liver cancer (miR-212: r_s = -0.709, P < 0.01; miR-132: r_s = -0.877, P < 0.01). Overexpression of miR-212 or miR-132 in HepG2 cells significantly inhibited the activity and expression of 3’-UTR, and interference of miR-212 or miR-132 significantly increased the activity and expression of 3’-UTR in GP73. Overexpression of GP73 reversed the reduction in survival rate of hepatoma cells induced by the overexpression of miR-212 or miR-132. Conclusion Patients with liver cancer have a significant reduction in the expression of miR-212 and miR-132 in serum, which is closely associated with the development, progression, and metastasis of liver cancer, and miR-212 and miR-132 in hepatoma cells inhibit the growth of liver cancer by targeted regulation of GP73 expression.