Despite breakthroughs in immunotherapy for solid tumors, significant variations in treatment efficacy persist. Up to 80% of cancer patients suffer from malnutrition, which leads to: lymphoid atrophy and reduced T-cell reserves; deficiency of substrates required for T-cell activation and expansion; concurrent inflammation hindering T-cell infiltration into tumors; and cachexia accelerating PD-1 antibody clearance. Clinical studies confirm that severe malnutrition significantly impairs immune responses and increases the risk of treatment toxicity. Therefore, implementing standardized nutritional therapy is crucial for optimizing the reserve, activation, expansion, and infiltration capacity of immune cells, thereby providing a sound immune system foundation for immunotherapy. Immunonutrition therapy, by enhancing immunonutrients such as arginine, omega-3 polyunsaturated fatty acids, and nucleotides, reduces the secretion of pro-inflammatory mediators and promotes T-cell activation and proliferation. This enhances anti-tumor immune responses, prolongs survival, and advances cancer treatment towards multimodal combination and precision approaches.

Background Lung cancer, one of the most common malignant tumors worldwide, has long ranked first in cancer incidence and mortality, posing a severe challenge to public health systems. Objective To analyze the trends in incidence, mortality, and disability-adjusted life years (DALYs) of lung cancer among residents in Jing'an District, Shanghai, from 2002 to 2021, explore the impacts of population aging, population growth, and age-specific prevalence on disease burden, and provide a scientific basis for optimizing regional lung cancer prevention and control strategies. Methods Based on the cancer registration and cause-of-death surveillance data of registered residents in Jing'an District, Shanghai, from 2002 to 2021, Joinpoint regression models were used to analyze the annual change trends (APC) and average annual change trends (AAPC) of lung cancer incidence, mortality, DALY rate, and their age-standardized rates. Decomposition analysis was applied to quantify the contribution of population aging, population growth, and age-specific prevalence to changes in the number of new cases, deaths, and DALYs. Results From 2002 to 2021, the crude incidence rate of lung cancer in Jing'an District increased from 68.00 per 100000 to 144.36 per 100000 (AAPC=4.86%, P<0.001), and the age-standardized incidence rate rose from 43.09 per 100000 to 61.46 per 100000 (AAPC=2.89%, P<0.001). The growth rate of incidence was significantly higher in females (AAPC=6.73%) than in males (AAPC=3.62%). The crude mortality rate increased from 58.08 per 100000 to 66.11 per 100000 (AAPC=1.10%, P<0.001), while the age-standardized mortality rate decreased (AAPC=−1.54%, P<0.001). The crude DALY rate showed an upward trend (AAPC=0.94%, P=0.002), whereas the age-standardized DALY rate declined (AAPC=−1.63%, P<0.001). Significant differences were observed across genders and age groups: the mortality and DALY rates increased in males aged 60-64 years, while the fastest incidence growth occurred in females aged 45-64 years. The results of decomposition analysis indicated that the increase in new cases was primarily attributed to age-specific incidence (38.15%) and aging (37.31%); the growth in deaths and DALYs was driven by aging, while age-specific mortality and population growth showed offsetting effects. From 2002 to 2021, the probability of premature death from lung cancer among males (2.04%-2.52%) in Jing'an District showed no statistically significant trend (AAPC=−0.28%, P=0.440), while it presented a decreasing trend in the total population (1.37%-1.89%) and females (0.72%-1.26%) (AAPC=−0.80% and −2.23%, respectively; P=0.029 and <0.001, respectively). Conclusion From 2002 to 2021, the risk of lung cancer incidence in Jing’an District, Shanghai, continue to increase, with a disease burden exhibiting significant heterogeneity by gender and age: key features include a rapid increase in new cases and a trend toward younger onset among females, alongside rising mortality risk among males aged 60–64 years. Population aging and increasing age-specific incidence rates are primary drivers of the growing number of cases, while declining age-specific mortality rates mitigate the rise in mortality burden.

Objective : To investigate the effects of branched-chain amino acid(BCAA) on the differentiation of 3T3-L1 preadipocytes and its potential mechanism. Methods : 3T3-L1 preadipocytes were divided into the Control, differentiation medium(DM), low-concentration BCAA, and high-concentration BCAA groups. A CCK-8 assay was utilized to evaluate pre-adipocyte survival under various BCAA concentrations. Oil-red O staining was used to observe the formation of lipid droplets in adipocytes. Intracellular triglyceride(TG) and total cholesterol(TC) were detected by enzymatic method. RT-qPCR and Western blot were used to detect the mRNA and protein expression of Stat3 and adipocyte differentiation-related genes. Results : CCK-8 results showed that the viability of 3T3-L1 cells was not affected when the BCAA concentration was ≤ 10 mmol/L. Compared with the DM group, the low-concentration BCAA groups(0.5 and 1.0 mmol/L) had significantly larger intracellular lipid droplets, increased number of lipid droplets, and elevated levels of the intracellular TC(0.88vs0.68 mmol/g; 0.83vs0.68 mmol/g,P<0.01) and TG(0.77vs0.40 mmol/g; 0.62vs0.40 mmol/g,P<0.01). Nevertheless, the cell differentiation in the high-concentration group(5.0 and 10.0 mmol/L) significantly decreased compared with that in the DM group. Further, levels of PPARγ, C/EBPα, Adiponectin, and FABP4 mRNA and protein expression significantly increased in the low-concentration group, but significantly decreased in the high-concentration group than that in the DM group(P<0.01). In addition, low concentrations of BCAA promoted stat3 phosphorylation, while high concentrations inhibited its phosphorylation(P<0.01). Conclusion BCAA have a dual role in regulating the differentiation of preadipocytes through Stat3, i.e. low concentrations of BCAA induce cell differentiation by promoting Stat3 phosphorylation; whereas high concentrations of BCAA inhibit Stat3 phosphorylation and cell differentiation.

Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

Objective:To identify the prognostic value of the Revised 15-item Myelodysplastic Syndrome-specific frailty scale (FS-15) in Chinese patients with myelodysplastic syndromes (MDS) .Methods:This retrospective study analyzed 812 patients with newly diagnosed MDS admitted to the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College from August 2016 to June 2023. Patients were assessed using the FS-15 and subsequently categorized into frail and non-frail groups. Clinical and laboratory characteristics, as well as overall survival (OS), were compared between these groups.Results:① The median patient age was 55 years ( IQR 45–64), with a median follow-up of 22.5 months (95% CI: 20.2–24.9) and a median OS of 43.3 months (95% CI: 36.8–49.8). The median FS-15 score was 0.42, with a cutoff value of 0.44. Male patients demonstrated higher median FS-15 scores than female patients (0.42 vs 0.38, P=0.006). In both the Revised International Prognostic Scoring System (IPSS-R; P=0.001) and Molecular International Prognostic Scoring System (IPSS-M; P=0.014) stratifications, FS-15 scores were significantly higher in the very high-risk group compared with the very low-risk group. ② The median OS was 54.7 months (95% CI: 47.5–NA) and 31.5 months (95% CI: 22.9–41.0) in the nonfrail ( n=452) and frail groups ( n=360), respectively ( P<0.001). The 3-year OS rates were (63.2 ± 3.2) % and (46.4 ± 3.6) % for the non-frail and frail groups, with 5-year OS rates of (49.9 ± 4.7) % and (32.0 ± 4.3) %, respectively ( P<0.001). ③Subgroup analysis revealed that nonfrail patients demonstrated significantly higher 3-year OS rates than frail patients in both the IPSS-M low-risk and very high-risk groups (all P<0.05). Similarly, nonfrail patients demonstrated superior 3-year OS rates compared with frail patients in the IPSS-R very low-risk, low-risk, and high-risk groups (all P<0.05). ④Among patients receiving hypomethylating agent therapy, the overall response rate was significantly higher in the non-frail group than in the frail group (86.7% vs 64.6%, P=0.007). Moreover, the frail group experienced higher rates of treatment-related adverse events, including febrile neutropenia (67.1% vs 47.4%, P=0.016) and liver function abnormalities (30.0% vs 14.5%, P=0.023), compared with the non-frail group. Conclusion:The FS-15 frailty score is a feasible and effective tool for assessing frailty in patients newly diagnosed with MDS in China and serves as a valuable prognostic indicator.

Therapeutic cancer vaccines have experienced a resurgence over the past ten years. Cancer vaccines are typically designed to enhance specific stages of the cancer-immunity cycle, primarily by activating the immune system to promote tumor regression and overcome immune resistance. In this review, we summarize the significant recent advancements in cancer immunotherapy based on the cancer-immunity cycle, including the effector cell function, infiltration, initiation, and exhaustion. We summarize the identification of tumor antigens and their delivery through cancer vaccines. We discuss how specific stages of the cancer-immunity cycle have been leveraged to augment anti-tumor immune responses and improve vaccine efficacy. Additionally, the impact of aging and myelosuppression, two prevalent forms of immunological stress, on the effectiveness of therapeutic cancer vaccines is deliberated. Finally, we summarize the current status of various therapeutic cancer vaccines at different clinical trial phases.
Humans ; Cancer Vaccines/therapeutic use* ; Neoplasms/therapy* ; Immunotherapy/methods* ; Antigens, Neoplasm/immunology* ; Animals

OBJECTIVE To explore the effect of Jinkui shenqi pill and its potential mechanism on diabetic nephropathy-related osteoporosis （DNOP） in rats. METHODS The rats were randomly divided into blank control group， control group， model group， Jingui shenqi pill low-， medium- and high-dose groups （0.62， 1.24， 2.48 g/kg）， and positive control group （denosumab 3 mg/ kg）， with 12 cases in each group. Except for the blank control group and the control group， models of DNOP were constructed in the remaining groups by high-glucose and high-fat forage， 3% fructose solution for feeding+intraperitoneal injection of streptozotocin solution. At 2 d after successful molding， Jingui shenqi pill low-， medium- and high-dose groups， and positive control group were given intragastric administration or subcutaneous injection of the corresponding drugs， once a day， for consecutive 8 weeks. After the last administration， bone mineral density （BMD） and serum bone metabolism-related indexes [osteocalcin （OC）， calcium， phosphorus， alkaline phosphatase （ALP）， tartrate-resistant acid phosphatase （TRAP）] were detected. The pathological changes of right femoral tissues were observed， and the expressions of receptor activator of NF-κB ligand （RANKL）/receptor activator of NF-κB （RANK）/osteoprotegerin （OPG） pathway-related mRNAs and proteins in left femoral tissues were detected. RESULTS Compared with the blank control group and the control group， there was rupture of bone trabecula and severe structural damage in the model group， and tissue space was obvious. BMD and ALP activities， mRNA and protein expressions of OPG were significantly decreased or down-regulated， while the levels of OC， calcium and phosphorus， TRAP activity， mRNA and protein expressions of RANKL and RANK were significantly increased or up-regulated （P＜0.05）. Compared with the model group， the number of bone trabeculae was increased in all Jingui shenqi pill groups， and the arrangement of bone trabeculae was more regular and dense. The above indexes generally were improved in a certain dose-dependent manner （P＜0.05）. CONCLUSIONS Jingui shenqi pill can promote osteogenesis and regulate the balance of bone metabolism in DNOP rats， which may be related to down-regulating the expressions of RANKL and RANK， and up-regulating the expression of OPG.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

ObjectiveTo observe the clinical efficacy of Tongfu Kuanzhong decoction （TFKZ） in the treatment of constipation-predominant irritable bowel syndrome （IBS-C） with spleen deficiency and Qi stagnation and its effects on anorectal manometry and colonic electrical activity parameters. MethodsSixty-four patients with IBS-C of the spleen deficiency and Qi stagnation type were included as research subjects and were randomized into the observation group （thirty-two cases） and control group （thirty-two cases）. The control group was orally administered mosapride citrate tablets， and the observation group was orally administered TFKZ. Both groups were treated for 4 weeks. The traditional Chinese medicine （TCM） syndrome scores， patient assessment of constipation symptoms （PAC-SYM） score， general anxiety disorder-7 （GAD-7） score， patient health questionnaire-9（PHQ-9）score， anorectal manometry， and colonic electrical activity parameters were observed before and after treatment in the two groups. ResultsThe total points of TCM syndromes were significantly lower in both groups after treatment （P<0.01） and lower in the observation group （P<0.05）. The fecal symptoms， rectal symptoms， abdominal symptoms， and total symptom scores of the patients in both groups were significantly decreased after treatment （P<0.01）， and the rectal symptoms， abdominal symptoms， and total symptom scores of the observation group were lower （P<0.05，P<0.01）. In both groups， the forced anal residual pressure and the initial rectal sensation threshold decreased after treatment （P<0.05，P<0.01）， and forced anal residual pressure in the control group was lower （P<0.01）. After treatment， the GAD-7 and PHQ-9 scores of patients in both groups decreased significantly （P<0.01）， and the GAD-7 score of the observation group was significantly lower （P<0.01）. After treatment， the average wave amplitude at different time points of each lead increased significantly in both groups， compared with that before treatment （P<0.01）. The average wave amplitude of each lead of the ascending colon， descending colon， sigmoid colon， and rectum in the observation group at 5 min before the meal and 10 min after the meal， as well as that of the ascending colon and rectum at 20 min and 30 min after the meal， was higher than that of the control group （P<0.05）. ConclusionTFKZ is effective in the treatment of IBS-C. Its mechanism may be related to the regulation of colonic function by down-regulating the forced anal residual pressure and the initial rectal sensation threshold and up-regulating the amplitude and frequency of intestinal electrical activity in each intestinal segment of the colon.