Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer-immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer-immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.

Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8⁺ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.

[This corrects the article DOI: 10.1016/j.apsb.2023.04.002.].

Objective:To analyze the correlation between the body composition and cardiorespiratory fitness (CRF) decline in physical examination population of different genders.Methods:Clinical data of the cardiopulmonary exercise testing (CPET) and body composition analysis of 439 people who received physical examination in the Medical Examination Center of Peking University Third Hospital from May 2021 to September 2021 were retrospectively analyzed. The general data, physical examination, biochemical parameters, body composition and CPET results were collected. The subjects were divided into normal group and decline group according to the percentage of peak oxygen uptake (VO 2peak) levels ≥ 85% or<85%. Multivariate logistic regression was applied to investigate the influencing factors of CRF decline in subjects of different genders. Results:Among men, total cholesterol and triglyceride in the decline group were significantly higher than those in the normal group [(5.097±0.890) vs (4.865±0.856) mmol/L, (1.778±1.200) vs (1.485±0.709) mmol/L], and the blood homocysteine (Hcy) and skeletal muscle index were significantly lower than those in the normal group [13.00 (11.30, 15.90) vs 13.80 (12.05, 17.10) μmol/L, (7.89±0.65) vs (8.08±0.64) kg/m 2] (all P<0.05). Among women, skeletal muscle index in the decline group was significantly lower than that in the normal group [(6.21±0.52) vs (6.53±0.56)kg/m 2], and percent body fat was significantly higher than that in the normal group [(32.83±4.92)% vs (31.21±4.55)%] (all P<0.05). The elevation of triglyceride level ( OR=1.487, 95% CI: 1.042-2.121) and visceral fat area ( OR=1.032, 95% CI: 1.014-1.051) were positively correlated with the decline of CRF in man, the decrease of skeletal muscle index ( OR=0.215, 95% CI: 0.106-0.435) and the increase of percent body fat ( OR=1.149, 95% CI: 1.060-1.245) were positively correlated with the decrease of CRF in women (all P<0.05). Conclusions:There is a correlation between body composition and CRF decline in physical examination population of different genders. Men should control visceral fat more effectively, and women should pay attention to increase muscle mass while reducing body fat, in order to improve CRF.

Objective:To evaluate the use of serosa muscular layers circumferential incision combined with mucosal layer cutting and closure by laparoscopic or robotic surgery for gastrointestinal mesenchymal tumors at difficult sites of the stomach.Methods:From Jul 2019 to Apr 2021, 18 gastric mesenchymal tumor patients undergoing serosa muscular layers circumferential incision combined with mucosal layer cutting and closure by laparoscopic or robotic surgery at the Department of Surgery, the Fourth Hospital of Hebei Medical University were retrospectively analyzed.Results:All 18 patients had successful surgery, including 7 cases of robotic surgery, 11 cases of laparoscopic surgery, and there was no conversion to open surgery. Tumors were at the gastric in cardia, 8 cases at the gastric body and lesser curvature in 4 cases, and at the gastric antrum in 6 cases, respectively. Eleven cases were of endogenous and 7 cases were of dumbbell type. The average operation time was (99±29) min, the intraoperative blood loss was (10±5) ml, the first time taking food per mouth was (2.0±1.0) d, and the postoperative hospital stay was (4.9 ± 1.2) d. Pathology showed gastrointestinal stromal tumor in 11 cases, leiomyoma in 5 cases and schwannoma in 2 cases. All were with negative margins. The average tumor diameter was (4.7±1.4) cm. The median follow-up time was 16.5 months, and there was no sign of tumor recurrence or metastasis.Conclusion:The serosa muscular layers circumferential incision combined with mucosal layer cutting and closure technique in laparoscopic or robotic surgery is a safe and feasible procedure for treating gastrointestinal mesenchymal tumor at difficult sites of the stomach.

Objective:To analyze the core elements′ index design of physical examination reports and pilot data.Methods:We searched and analyzed the core element indexes of the physical examination report in databases such as CNKI and Wanfang through the literature analysis method, forming the initial core element indicator set. Special working meetings were organized to discuss revisions and improvements. The core elements′ index set was formed using a mixed research method combined with the quantitative analysis results of pilot data and expert opinions. Six hundred and thirteen cases from five hospitals were included in this study, including Anzhen Hospital, Peking University Third Hospital, Beijing Physical Examination Center, Beijing Tongren Hospital, China-Japan friendship hospital.Results:The subjects were (49.5±17.6) years old, including 302 males (49.3%) and 311 females (50.7%). The physical examination conclusion indicates that the number of health problems is between five and eight, with no significant difference between men and women. The health history data analysis of different sexes showed that hypertension in men was significantly higher than in women (17.9% vs. 10.6%, P=0.010). The lifestyle and eating habits survey showed that men had significantly higher incidences of smoking and drinking than women (24.8% vs. 2.2%, P?0.001; 9.9% vs. 1.3%, P?0.001). The exercise habits and sleep survey showed that the proportion of men who did not exercise was lower than that of women (13.2% vs. 22.8%, P=0.022). There was no statistically significant difference in sleep duration between the sexes. Conclusions:The core elements of health examination reports can standardize the collection of physical examination data and improve its sharing and application. This can allow the reports to better assist the decisions based upon physical examination report data.

Objective:To investigate the influence of different injection time of carbon nanoparticle tracer on the acquisition of lymph nodes in adenocarcinoma of esophagogastric junc-tion (AEG) treated by neoadjuvant chemoradiotherapy (nCRT) combined with surgical resection.Methods:The prospective randomized controlled study was conducted. The clinicopathological data of 120 AEG patients who were treated by nCRT combined with surgical resection in the Fourth Hospital of Hebei Medical University from March 2020 to March 2021 were selected. Based on random number table, patients were allocated into two groups. Patients undergoing endoscopic injection of carbon nanoparticle tracer 24 hours before nCRT were allocated into the experiment group, and patients undergoing endoscopic injection of carbon nanoparticle tracer 24 hours before surgical resection were allocated into the control group. All patients received the same plan of nCRT combined with D 2 radical gastrectomy. Observation indicators: (1) grouping situations of the enrolled patients; (2) surgical and postoperative pathological situations; (3) postoperative complications and treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement date with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Results:(1) Grouping situations of the enrolled patients. A total of 120 patients were selected for eligibility. There were 85 males and 35 females, aged (60±9)years. There were 60 patients in the experiment group and 60 patients in the control group, respectively. (2) Surgical and postoperative pathological situations. Patients in the two groups underwent D 2 radical gastrectomy successfully, with R 0 resection. The number of lymph nodes harvest, the number of lymph nodes stained, the number of metastatic lymph nodes stained, the number of micro lymph nodes, the number of inferior mediastinal lymph nodes, the number of inferior mediastinal lymph nodes stained, cases in postoperative pathological stage N0, stage N1, stage N2, stage N3a were 40.6±13.9,20.1±7.7, 1.0(0,3.0), 8.1±2.8, 3.7±1.3, 2.0(1.0,2.0), 18, 13, 23, 6 in patients of the experiment group, respectively. The above indicators were 30.4±8.3, 12.7±3.5, 0(0,1.0), 6.2±2.0, 2.4±1.2, 1.0(0,1.0), 23, 21, 15, 1 in patients of the control group, respectively. There were significant differences in the above indicators between the two groups ( t=-5.01, 6.85, Z=-3.78, t=-4.04, -5.57, Z=-5.48, -2.12, P<0.05). (3) Postoperative complications and treatment. There were 5 cases of the experiment group and 7 cases of the control group with postoperative complications, showing no significant difference between the two groups ( χ2=0.37, P>0.05). The patients with postoperative complications were improved after symptomatic treatment. Conclusion:Compared with injection of carbon nanoparticle tracer 24 hours before surgical resection, injection of carbon nanoparticle tracer 24 hours before nCRT can improve the acquisition of lymph nodes in AEG treated by nCRT combined with surgical resection.

Objective To investigate the clinicopathological characteristics and prognosis of patients with Borrmann type Ⅳ gastric cancer. Methods A cohort retrospective analysis of 2386 patients with gastric cancer who underwent radical surgery was used to screen out Borrmann type Ⅳ patients, and analyze their clinical features and prognostic factors. Results Among 2386 patients with gastric cancer, 363 cases (15.21%) were Borrmann type Ⅳ. Compared with non-Borrmann type Ⅳ gastric cancer patients, Borrmann type Ⅳ patients had higher rates of simultaneous liver metastasis, metachronous liver metastasis, lymph node metastasis and vascular infiltration. Moreover, the age of onset tended to be younger and the pathological type tended to be poorly differentiated-undifferentiated (all P < 0.05). The 5-year OS of the entire group was 49.32% and the 5-year DFS was 44.61%. There were significant differences in 5-year OS and DFS between Borrmann type Ⅳ and non-Borrmann type Ⅳpatients (all P < 0.001). The subgroup analyses showed that there were statistically significant differences in 5-year OS and DFS of gastric cancer patients between Borrmann type Ⅳ and non-Borrmann type Ⅳ in pT2-pT4a and pN0-pN3a stages (all P < 0.005). Multivariate analysis showed that the poorly differentiated-undifferentiated tumor, the T4a-pT4b stage of tumor invasion depth, lymph node metastasis, the ⅢA-ⅢC pTNM stage of the tumor, postoperative liver metastasis and peritoneal metastasis were independent risk factors affecting the prognosis of Borrmann type Ⅳ gastric cancer patients (all P < 0.05). Conclusion Borrmann type Ⅳ gastric cancer is prone to liver metastasis, lymph node metastasis, peritoneal metastasis and poor prognosis, and it's prognosis is affected by a variety of independent risk factors.

Objective:To investigate the application value of individualized full-course nutritional intervention in neoadjuvant concurrent chemoradiotherapy (nCRT) for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The perspec-tive randomized control study was conducted. The clinicopathological data of 90 patients with locally advanced Siewert type Ⅱ and Ⅲ AEG who underwent nCRT in the Fourth Hospital of Hebei Medical University from February 2012 to December 2018 were selected. Patient were divided into two groups with 1:1 according to random number table. Patients undergoing nCRT combined with individualized full-course nutritional intervention were allocated into experimental group, and patients undergoing nCRT combined with common nutritional intervention were allocated into control group. Observation indicators: (1) grouping situations of the enrolled patients; (2) changing situations of nutritional status and quality of life of patients in nCRT and preoperative waiting period; (3) efficacy evaluation and adverse effects of nCRT; (4) surgical and recovery situations. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement date with skewed distribution were represented as M ( P25, P75) or M (range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were represented as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Grouping situations of the enrolled patients: a total of 90 patients were selected for eligibility. There were 77 males and 13 females, aged from 26 to 74 years, with a median age of 62 years. Of 90 patients, there were 45 cases in the experimental group and 45 cases in the control group. (2) Changing situations of nutritional status and quality of life of patients in nCRT and preoperative waiting period: ① during the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the body mass was (67±10)kg, (66±9)kg, (67±10)kg, (68±10)kg, (70±10)kg for the experi-mental group, respectively, and (65±9)kg, (59±8)kg, (62±8)kg, (64±8)kg, (66±9)kg for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the body mass ( χ2=195.010, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of body mass changing between the two groups ( F=93.974, 60.638, 4.144, P<0.05). ② During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the total protein was (66±4)g/L, (65±4)g/L, (65±4)g/L, (68±4)g/L, (71±5)g/L for the experimental group, respectively, and (65±4)g/L, (62±5)g/L, (63±5)g/L, (65±5)g/L, (67±6)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the total protein ( χ2=652.524, P<0.05). There were significant differences in the time effect, interaction effect, interven-tion effect of total protein changing between the two groups ( F=672.507, 6.424, 5.057, P<0.05). ③ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the albumin was (40±3)g/L, (38±4)g/L, (38±4)g/L, (39±4)g/L, (40±4)g/L for the experimental group, respectively, and (39±4)g/L, (35±5)g/L, (36±4)g/L, (36±4)g/L, (37±5)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the albumin ( χ2=289.324, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of albumin changing between the two groups ( F=4 210.683, 5.013, 7.330, P<0.05). ④ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the prealbumin was (228±41)mg/L, (222±56)mg/L, (223±47)mg/L, (227±46)mg/L, (233±53)mg/L for the experimental group, respectively, and (202±49)mg/L, (174±68)mg/L, (179±54)mg/L, (185±51)mg/L, (193±57)mg/L for the control group. The multi-variate test was conducted based on the mauchly's test of sphericity for the prealbumin ( χ2=297.324, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of prealbumin changing between the two groups ( F=871.545, 6.111, 14.426, P<0.05). ⑤ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the hemoglobin was (124±14)g/L, (121±14)g/L, (125±13)g/L, (127±13)g/L, (128±13)g/L for the experimental group, respectively, and (121±18)g/L, (114±14)g/L, (116±14)g/L, (117±16)g/L, (118±22)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the hemoglobin ( χ2=257.560, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of hemoglobin changing between the two groups ( F=2 533.553, 4.142, 4.985, P<0.05). ⑥ During the nCRT treatment (week 3, week 6) and the preopera-tive waiting period (week 9, week 12, week 15), the patient-generated subjective global assessment (PG-SGA) score was 4.4±1.2,6.3±1.4, 5.5±1.4, 4.3±1.4, 3.4±1.7 for the experimental group, respec-tively, and 4.9±1.2, 7.4±1.7, 7.3±1.6, 6.3±1.4, 6.0±1.5 for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the PG-SGA score ( χ2=289.543, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of PG-SGA score changing between the two groups ( F=648.583, 41.906, 26.098, P<0.05). ⑦ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the quality of life questionnaire of stomach (QLQ-ST022) score was 13±3, 16±6, 16±4, 14±4, 12±5 for the experimental group, respectively, and 15±4, 21±6, 20±4, 17±4, 15±5 for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the QLQ-STO22 ( χ2=279.865, P<0.05). There were significant differences in the time effect, interaction effect, interven-tion effect of QLQ-STO22 changing between the two groups ( F=710.238, 7.261, 16.794, P<0.05). (3) Efficacy evaluation and adverse effects of nCRT: there were 25 patients and 20 cases of the experimental group with partial response and stable disease, showing the objective response rate and disease control rate as 55.6%(25/45)and 100.0%(45/45). There were 18 patients and 27 cases of the control group with partial response and stable disease, showing the objective response rate and disease control rate as 40.0%(18/45)and 100.0%(45/45). There was no significant difference in the nCRT efficacy between the two groups ( P>0.05). Cases with leukopenia, neutropenia, anemia, nausea, and loss of appetite were 27, 25, 19, 30, 34 for the experimental group, versus 37, 34, 29, 39, 42 for the control group, showing significant differences between the two groups ( χ2=5.409, 3.986, 4.464, 5.031, 5.414, P<0.05). (4) Surgical and recovery situations: patients of the experimental group underwent surgeries successfully. Two patients of the control group diagnosed with peritoneal metastasis after laparoscopic exploration underwent conversion therapy and no surgery, the other 43 patients underwent surgeries. The time to postoperative gastric tube removal, time to postopera-tive drainage tube removal, time to postoperative first flatus, time to postoperative first defecation, duration of postoperative hospital stay were 2.0 days (1.5 days, 3.0 days), 6.0 days (5.0 days,11.0 days), 2.0 days (1.5 days, 2.5 days), 2.0 days (1.5 days, 2.5 days), 7.0 days (6.0 days,14.0 days) for the experimental group, versus 3.0 days (2.0 days,4.0 days), 7.0 days (5.5 days,14.0 days), 2.0 days (1.5 days,3.0 days), 3.0 days (2.0 days,3.5 days), 8.0 days (6.0 days, 17.0 days) for the control group, showing significant differences between the two groups ( Z=-3.477, -4.398, -3.068, -5.786, -3.395, P<0.05). Conclusion:For AEG patients undergoing nCRT, the individualized full-course nutrition intervention involving nutritionists is beneficial to improve the nutritional status, reduce adverse reactions, and improve the quality of life of the patients, promote postoperative short-term recovery. Registry: this study was registered at clinicaltrials.gov in United States, with the registry number of NCT01962246.

Objective:To investigate the correlation between early renal impairment markers in urine and elevated serum homocysteine.Methods:Clinical data of serum homocysteine (Hcy) and early renal injury markers in urine of the health examination population from the Physical Examination Center of Peking University Third Hospital from January 2019 to May 2020 were retrospectively analyzed (1133 cases). The previous medical history, age, sex, blood pressure, body mass index (BMI) of the subjects were collected. Early urine kidney injury markers, including urine microalbumin (U-mALB), urinary N-acetyl-β-D-glucosaminidase (NAG), urinary albumin to creatinine ratio (UACR), and serum renal function, liver function, blood lipid, myocardial enzyme and glycosylated hemoglobin (HbA 1C), etc. were also collected. Those with incomplete previous history, general information, biochemical indexes and decreased estimated glomerular filtration rate (eGFR) were excluded, and 969 cases were included. The included subjects were divided into the normal group (?15 μmol/L) and the elevated group (≥15 μmol/L) according to Hcy levels, the indexes with significant difference between the two groups were included as independent variables, and the multivariate logistic regression was used to explore the influence factors of Hcy elevation. Results:The male ratio, the incidence of increased U-mALB, NAG and UACR were significantly higher in the elevated group than those in the normal Hcy group (93.4% vs 50.6%, 16.4% vs 8.0%, 23.0% vs 14.0%, 13.9% vs 7.9%) (all P<0.05). Systolic blood pressure, diastolic blood pressure, serum uric acid, calcium, alanine aminotransferase (ALT) and lactate dehydrogenase in the elevated group were higher than those in the normal group [(127.5±15.4) vs (121.9±16.2) mmHg (1 mmHg=0.133 kPa), (78.6±9.3) vs (76.0±11.0) mmHg, (385.9±86.0) vs (335.7±88.2) μmol/L, (2.392±0.086) vs (2.366±0.092) mmol/L, (27.8±21.0) vs (23.8±20.2) U/L, (198.3±28.4) vs (192.2±31.2) U/L] (all P<0.05), while high density lipoprotein cholesterol (HDL-C), serum phosphorus were lower than those in the normal group [(1.21±0.25) vs (1.31±0.30) mmol/L, (1.107±0.154) vs (1.158±0.159) mmol/L] (all P<0.05). The increased systolic blood pressure, male, uric acid, U-mALB, NAG were independent correlative factors of Hcy elevation. Conclusion:The increase of Hcy is independently correlated with urine U-mALB and NAG, which suggests that the level of Hcy should be detected as soon as possible in patients with elevated early renal injury markers.