ObjectiveTo explore the effects of genetic variation of obesity-related biological pathways and gene-obesity interactions on the incidence of gastric cancer, so as to better understand the pathogenesis of gastric cancer and help identify high-risk populations for individualized prevention of gastric cancer. MethodsA case-control study based on the Shanghai Suburban Adult Cohort and Biobank study (SSACB) was conducted on the cases with gastric cancer. A total of 267 cases with gastric cancer and 267 healthy controls matched 1∶1 by age and gender using propensity score were included in the study. After genome-wide genotyping, quality control and imputation, 19 250 single nucleotide polymorphism (SNP) sites from 115 genes in 4 obesity-related biological pathways were extracted. Univariate and multivariate logistic regression analyses were used to evaluate the association between these SNP sites and the risk of gastric cancer, and false positive report probability (FPRP) was used for multiple test correction.Data from Biobank Japan (BBJ) and FinnGen public accessible databases were used to validate significant SNP sites. For validated sites, expression quantitative trait loci (eQTL) analysis and differentially expressed genes analysis were further performed. Additive and multiplicative interactions were used to evaluate the gene-obesity interactions on the incidence of gastric cancer. Additive interaction evaluation indicators included relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (SI), while multiplicative interaction evaluation indicators include OR_GxE and P_inter. ResultsA total of 41 SNP sites were significantly associated with the onset of gastric cancer (P_adj<0.05, FPRP_0.1<0.1), among which 7 groups of haplotype blocks were formed. ACACB/ rs2268401 [SSACB: P=0.005, BBJ: P=0.049], HRAS/ rs12785860 (SSACB: P<0.001, FinnGen: P=0.045), and PTPN1/ rs6095985 (SSACB: P<0.001, FinnGen: P=0.023) were significantly associated with the risk of gastric cancer after validation in different populations. Among which, the G allele of HRAS/ rs12785860 was correlated with the downregulation of HRAS mRNA expression (P<0.001), and the expression level of HRAS in gastric cancer tissues was higher than that in adjacent normal tissues (P<0.001). Additionaly, JAK1/rs11208559 showed a positive additive interaction with waist circumstance (WC) on the risk of gastric cancer [RERI=2.29(0.06~4.53), AP=0.57(0.23~0.90), SI=4.03(2.20~5.87)]. ConclusionObesity-related biological pathway SNP sites and their haplotypes are associated with the risk of gastric cancer, suggesting that genetic variations in obesity pathways may affect gastric cancer. The HRAS/ rs12785860 is significantly associated with downregulation of HRAS gene expression, which may serve as a potential genetic marker for gastric cancer. JAK1/rs11208559 interacts with obesity additively on the risk of gastric cancer. Individuals with GC+CC genotypes and pre-central or central obesity have an increased risk of gastric cancer, providing clues and evidences for individualized prevention of gastric cancer.

Immunotherapy has been widely used in cancer treatment in recent years and functions by stimulating the immune system to kill tumor cells. Radiation therapy (RT) uses radiation to induce DNA damage and kill tumor cells. However, this activates the body's immune system, promoting the release of tumor-related antigens from inactive dendritic cells, which stimulates the recurrence and metastasis of tumors in immune system tissues. The combination of RT and immunotherapy has been increasingly evaluated in recent years, with studies confirming the synergistic effect of the two antitumor therapies. Particularly, the combination of RT by dose adjustment with different immunotherapies has positive implications on antitumor immunity as well as disease prognosis compared with respective monotherapies. This review summarizes the current research status, progress, and prospects of RT combined with immunotherapy in cancer treatment. It additionally discusses the prevalent concerns regarding the dose, time window, and toxicity of this combination therapy.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Combined Modality Therapy ; Radiotherapy/methods*

BACKGROUND: Lung cancer is one of the malignant cancers with the highest incidence rate, and it is important to identify the factors contributing to lung cancer carcinogenesis for prevention. Lifestyle and genetic factors play important roles in cancer development, however the impact of dietary factors, such as soy product intake, on lung cancer risk remains inadequately understood. This study aims to explore the associations between soy product intake, genetic risk, and lung cancer incidence, and validate the consistent effects of soy product intake in European populations, thereby providing new insights for lung cancer prevention. METHODS: Utilizing the Shanghai Suburban Adult Cohort and Biobank (SSACB) (n=66,311), Cox proportional hazards model was adopted to assess the association between soy product intake and lung cancer incidents, followed by subgroup analyses stratified by gender, smoking status, and pathological types of lung cancer. The UK Biobank (UKB) was used for validation of the effect of soy product intake on lung cancer. To investigate the association between genetic factors and lung cancer, in addition to previously reported loci, we incorporated newly identified loci from two independent studies in Southeast China: a nested case-control population from the SSACB cohort (433 cases/650 controls) and a case-control study from the Shanghai Cancer Center-Taizhou cohort (1359 cases/1359 controls). Meta-analysis and Linkage disequilibrium clumping (LD clumping) of the association results identified 23 loci for polygenic risk score (PRS) construction. Subsequently, conditional Logistic regression model was used to assess the association between genetic risk and lung cancer. RESULTS: In SSACB cohort, after adjusting for age, gender, smoking, chronic bronchitis, body mass index (BMI), vegetable intake and red meat intake, sufficient soy product intake was significantly associated with a reduced risk of lung cancer [hazard ratio (HR)=0.60, 95%CI: 0.47-0.77, Padj=6.69E-05], an effect that was consistent in males and females, smokers and non-smokers. In UKB, although the association did not reach statistical significance, a protective trend against lung cancer was also observed (HR=0.76, 95%CI: 0.55-1.06, Padj=0.10). In the nested case-control population within SSACB, a PRS score generated in the Chinese population was significantly correlated with lung cancer risk. After adjustment of age, gender, smoking, chronic bronchitis, and soy product intake, the high-PRS group had a 1.88 times higher risk of lung cancer compared to the low-PRS group (Padj=1.84E-03). CONCLUSIONS The prospective cohort study found that adequate intake of soy products was significantly associated with a reduced risk of lung cancer, while a high PRS is a risk factor for lung cancer development. Integrating soy product intake and PRS into traditional epidemiological risk factor prediction will guide personalized lung cancer prevention and high-risk population stratification.
Humans ; Lung Neoplasms/etiology* ; Male ; Female ; China/epidemiology* ; Middle Aged ; Adult ; Aged ; Prospective Studies ; Biological Specimen Banks ; Risk Factors ; Case-Control Studies ; Cohort Studies

The translocator protein (TSPO) positron emission tomography (PET) can noninvasively detect neuroinflammation associated with epileptogenesis and epilepsy. This study explored the role of the TSPO-targeting radioligand [¹⁸F]F-TFQC, an m-trifluoromethyl ER176 analog, in the PET neuroimaging of epileptic rats. Initially, [¹⁸F]F-TFQC was synthesized with a radiochemical yield of 8%-10% (EOS), a radiochemical purity of over 99%, and a specific activity of 38.21 ± 1.73 MBq/nmol (EOS). After determining that [¹⁸F]F-TFQC exhibited good biochemical properties, [¹⁸F]F-TFQC PET neuroimaging was performed in epileptic rats at multiple time points in various stages of disease progression. PET imaging showed specific [¹⁸F]F-TFQC uptake in the right hippocampus (KA-injected site, i.e., epileptogenic zone), which was most pronounced at 1 week (T/NT 1.63 ± 0.21) and 1 month (T/NT 1.66 ± 0.20). The PET results were further validated using autoradiography and pathological analysis. Thus, [¹⁸F]F-TFQC can reflect the TSPO levels and localize the epileptogenic zone, thereby offering the potential for monitoring neuroinflammation and guiding anti-inflammatory treatment in patients with epilepsy.

Objective To explore the influence of different hardness surfaces on gait coordination in patients with functional ankle instability(FAI). Methods Qualisys Infrared Optical Motion Capture System was used to test the coordination and variability of 15 FAI patients on the right side at Nanjing Normal University from May to July,2023.The gait cycle data were collect-ed and intercepted,and coupling angle(CA)and standard deviation of coupling angle(SDCA)were calculated by Matlab to compare the differences on different hardness surfaces. Results On coronal plane,CA of hip-ankle joint was higher on the hard surface than on the soft surface during middle stage of support and early stage of swing,and lower on its rest stages and the gait stages of hip-knee joint and knee-ankle joint than on the soft surface(P<0.01).On sagittal plane,CA of hip-ankle joint and knee-ankle joint was smaller on the hard surface than on the soft surface during middle and late stages of support,and larger than on the soft surface during their rest stages,and the gait stages of hip-knee joint(P<0.01).On horizontal plane,CA of hip-knee joint was lower on the hard surface than on the soft surface during the late stage of support,and higher than on the soft surface during its early stage of swing and bearing stage of hip-ankle joint(P<0.01).Compared with the hard surface,SDCA was smaller on the soft surface than on the hard surface only in the hip-ankle on the sagittal plane and during bearing stage of hip-knee joint,and was greater than on the hard surface for the rest(P<0.01). Conclusion FAI patients showed more distal dominance on soft surface than on hard surface during most gait cycle on 3D plane,i.e.,advantage of ankle varus and plantar flexion increased,and advantage of hip joint decreased;the coordination variability was generally higher on soft surface than on hard surface.These findings suggested that FAI patients may increase the risk of recurrent lateral ankle sprain walking on soft surface.

The BTB (broad-complex, tramtrack, and bric-à-brac) domain is a highly conserved protein interaction motif in eukaryotes. They are widely involved in transcriptional regulation, protein degradation and other processes. Recently, an increasing number of studies have shown that these genes play important roles in plant growth and development, biotic and abiotic stress processes. Here, we summarize the advances of these proteins ubiquitination-mediated development and abiotic stress responses in plants based on the protein structure, which may facilitate the study of this type of gene in plants.
Eukaryota ; Plant Development/genetics* ; Proteolysis ; Ubiquitination

Objective:To investigate the efficacy and safety of en-bloc Holmium laser enucleation of the prostate (HoLEP) with an early apical mucosa dissection technique for the treatment of benign prostate hyperplasia (BPH).Methods:The clinical data of 215 patients treated with HoLEP for BPH from January 2020 to January 2023 in the Department of Urology, Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. According to different treatment methods, the patients were divided into study group ( n=112) and control group ( n=103). Patients in the study group were treated by the en-bloc HoLEP with an early apical mucosa dissection technique, while patients in the control group were treated by the classical two or three-lobes HoLEP. The primary endpoints included the rates of urinary incontinence at 1-month, 3-month, and 6-month after surgery in two groups of patients. The secondary endpoints included operative time, hemoglobin decrease, dissected prostate weight, postoperative indwelling catheter time, postoperative hospital stay, and international prostate symptom score (IPSS), quality of life (QoL), Qmax, and postvoid residual urine (PVR) at 3-month and 6-month after surgery. The measurement data were tested by Shapiro-Wilk normality test. The normal distribution of the measurement data were expressed as mean ± standard deviation ( ± s), and independent sample t-test was used for comparison between two groups. Measurement data of skewness distribution were expressed as median (interquartile distance) [ M( Q1, Q3)], and Wilcoxon or Mann-Whitney U test were used for comparison between two groups. The count data in the two groups were compared by the Chi-square test. Results:The incidence of urinary incontinence in the study group was 9.0% (10/112) and 3.6% (4/112) at 1-month and 3-month after surgery, which was significantly lower than those in the control group [18.5% (19/103) and 11.7% (12/103)], and the differences were statistically significant ( P< 0.05). Urinary incontinence in two groups recovered completely 6-month after surgery. The operation time of the study group was (68.74±23.71) min, which was lower than that of the control group [(88.04±25.43) min], and the difference was statistically significant ( P<0.05). There were no significant differences in hemoglobin decrease, dissected prostate weight, postoperative indwelling catheter time, postoperative hospital stay in the two groups ( P> 0.05). The IPSS, QoL, Qmax and PVR of the two groups were significantly improved at 3-month and 6-month after surgery ( P< 0.05), but there was no significant difference between the two groups ( P> 0.05). Conclusion:En-bloc HoLEP with an early apical mucosa dissection technique is safe and reliable in treating BPH, and has advantages over classic HoLEP in terms of short-term urinary continence rates, shortening operation time.

Gastric cancer is the fifth most common cancer in the world, and chemotherapy is one of its main treatments. However, due to the side effects of chemotherapy drugs, about 87% of patients have malnutrition. Although the concept of nutrition therapy continues to advance, it still lacks sufficient attention, resulting in a low cure rate of malnutrition in gastric cancer patients. As an independent risk factor of death for gastric cancer patients, malnutrition not only leads to poor clinical outcomes, but also causes a huge social and economic burden. This review summarized the nutritional support treatment of gastric cancer patients undergoing chemotherapy in recent years, including the selection of nutrition evaluation tools, methods and effects of nutritional treatment, and made a prospect for its widespread clinical application in the future.

Objective:To analyze the clinical characteristics and genetic features of SMC1A gene related disorders. Methods:The data of 5 children with SMC1A gene variants were collected from Children′s Hospital of Fudan University from February 2018 to January 2022. The clinical features, electroencephalogram (EEG), brain imaging and gene testing results were summarized. Results:Among the 5 patients, 4 are females and 1 is male. Two female cases are siblings. One boy had dysmorphic features, consisting of bilateral ptosis, synophrys, a short nose and upturned nasal tip. He also had patent foramen ovale plus atrial septal defect, unilateral cryptorchidism and microcephaly. Three cases had microcephaly. Two girls had patent foramen ovale, and 2 girls had microcephaly. Four cases had epilepsy, and age at seizure onset ranged from 2 to 52 months. Multiple seizure types were observed, including bilateral tonic clonic seizures in 2 patients, and focal seizures in 3 patients. The seizures in 3 cases were in cluster. All patients had developmental delay, including 1 patient with mild and 4 patients with moderate to severe developmental delay. Three patients had slow background activity in EEG. Interictal EEG showed abnormal discharges in 4 patients, including focal discharges in 3 cases and generalized discharges in 1 case. Brain magnetic resonance imaging was normal in 3 patients and showed mild cortical thickening in 1 case. All cases harbored 4 SMC1A gene variants, including 2 missense variants and 2 frameshift variants (c.580_587del, c.2699delG, c.3362G>A, c.1486C>T). Three cases harbored heterozygous SMC1A variants and 2 cases carried somatic mosaic SMC1A variants with 17.5% and 88.1% mosaicism in peripheral blood. The follow-up lasted for 3 months to 4 years. The epilepsy was refractory in 2 cases. During the follow-up, all cases had very slow developmental progress or developmental retardation. All cases had different levels of growth retardation. The scores of Cornelia de Lange syndrome (CdLS) phenotypes in 5 cases were 2-6. One case had the combined phenotypes of atypical CdLS and developmental epileptic encephalopathy (DEE). The phenotype was atypical CdLS in 1 case and DEE in 1 case. The phenotypes of 2 cases with SMC1A missense variants were mild, manifesting as non-refractory epilepsy and moderate to severe developmental delay. Conclusions:All of cases with SMC1A gene variants have developmental delay. Most of the patients have clusters of seizures and some dysmorphisms. The phenotypes of SMC1A gene related disorders are diverse. Except CdLS and DEE, there are some patients with mild phenotype due to missense variants of SMC1A gene.

Objective:To investigate the efficacy and safety of en-bloc low-power (22.5 W) holmium laser for enucleation of prostate (LP-HoLEP) in the treatment of benign prostatic hyperplasia (BPH).Methods:The clinical data of 98 patients with BPH who underwent surgical treatment in the Department of Urology, Beijing Friendship Hospital, Capital Medical University from January 2020 to October 2022 were retrospectively analyzed. They were divided into LP-HoLEP group ( n=53) and TURP group ( n=45) according to different treatment methods. Patients in the LP-HoLEP group were treated with en-bloc holmium laser enucleation of prostate, and patients in the TURP group were treated with transurethral resection of prostate (TURP). Perioperative indexes of the two groups were compared, including operation time, postoperative hemoglobin changes, tissue resection amount, postoperative catheter indentation time, postoperative hospital stay, complications, and international prostate symptom score (IPSS), quality of life (Qol) score, maximum urine flow rate (Qmax), postvoid residual volume (PVR) and other indicators were obtained at 3 and 6 months after surgery. The measurement data were tested by Shapiro-Wilk normality test. The measurement data conforming to normal distribution were expressed as mean ± standard deviation ( ± s), independent sample t-test was used for comparison between groups, measurement data of skewness distribution were expressed as median (interquartile distance)[ M( Q1, Q3)], and Mann-Whitney U test was used for comparison between groups. The Chi-square test was used to compare the count data between groups. Results:In the LP-HoLEP group, the operative time was (65.74±22.82) min, the hemoglobin decreased 5.71(3.97, 9.01) g/L, the tissue resection volume was (60.59±24.40) g, and the catheter indinduration time was (3.03±0.91) d. The length of postoperative hospitalization was (4.14±1.05) d. TURP group was (77.04±27.33) min, 11.02(8.89, 16.51) g/L, (39.49±11.32) g, (4.80±0.91) d, (5.98±1.03) d, respectively. All the indexes of LP-HoLEP group were better than TURP group. The differences were statistically significant ( P<0.05). Compared with preoperative, IPSS, Qol score, Qmax and PVR of two groups were significantly improved at 3 months after surgery, but there were no statistical significance between groups ( P>0.05). Conclusion:En-bloc LP-HoLEP is safe and reliable in the treatment of BPH, and has advantages over TURP in terms of tissue resection volume, shortening hospitalization and indwelling catheter time, and reducing intraoperative bleeding.