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.

The application of pesticides(mostly insecticides and fungicides)during the tea-planting process will undoubtedly increase the dietary risk associated with drinking tea.Thus,it is necessary to ascertain whether pesticide residues in tea products exceed the maximum residue limits.However,the complex matrices present in tea samples comprise a major challenge in the analytical detection of pesticide residues.In this study,nine types of lateral flow immunochromatographic strips(LFICSs)were developed to detect the pesticides of interest(fenpropathrin,chlorpyrifos,imidacloprid,thiamethoxam,acet-amiprid,carbendazim,chlorothalonil,pyraclostrobin,and iprodione).To reduce the interference of tea substrates on the assay sensitivity,the pretreatment conditions for tea samples,including the extraction solvent,extraction time,and purification agent,were optimized for the simultaneous detection of these pesticides.The entire testing procedure(including pretreatment and detection)could be completed within 30 min.The detected results of authentic tea samples were confirmed by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),which suggest that the LFICS coupled with sample rapid pretreatment can be used for on-site rapid screening of the target pesticide in tea products prior to their market release.

Objective This study aims to optimize the evaluation index system for the Party branch work of a hospital,grounded on Party regulations,and employ diversified assessment methods to integrate Party branch development with the advance-ment of medical,educational,and research endeavors.Methods This study utilized literature review and textual analysis to identi-fy relevant documents.Through qualitative interviews and convenience sampling,25 questionnaires were distributed to Party repre-sentatives at all levels within the hospital,yielding 25 valid responses.The 5-point Likert scale was applied to rate and assess the importance of 74 selected assessment indicators.Results A comprehensive evaluation system was established,which includes 5 pri-mary indicators,14 secondary indicators,and 53 tertiary indicators.Conclusion The existing comprehensive quantitative assess-ment system for Party branches has been optimized.The adoption of diversified evaluation methods has led to a clearer,more explic-it,and standardized objectives for Party branch construction,thereby enhancing its guiding and motivational role.

Objective To analyze the clinical value of temperature-controlled ablation radio-frequency(TCAR)as a surgical option for the treatment of pediatric snoring.Method This study selected 120 children with snoring from January 2021 to December 2022 for observation.They were divided into the control group(n=60,receiving tonsil removal+nasal underopia gland scraping therapy)and the observation group(n=60,using TCAR to remove patients with gland samples and tonsils)using a random number table method.The clinical efficacy,surgery-related situation and sleep quality were compared.Results The effective rate of observation group was 93.33%,which was significantly higher than 76.67%of the control group.The intraoperative blood loss in the observation group was less than that in the control group,the operation time,symptom remission time and hospital stay were shorter,and the VAS was lower than those in the control group,with statistical significance(P<0.05).There was no statistically significant difference in the comparison of Quebec sleep questionnaire(QSQ)score,Epworth sleepiness scale(ESS),and disease specific quality of life for children with obstructive sleep apnea 18 items survey(OSA-18)between the two groups of patients before surgery(P>0.05);The postoperative ESS and OSA-18 of the observation group were lower than those of the control group,while the QSQ score was higher than that of the control group,with statistical significance(P<0.05).After surgery,the QSQ scores of the two groups were higher than before surgery,while the ESS and OSA-18 of the two groups were lower than before surgery,with statistical significance(P<0.05).The postoperative complications in the observation group(1.67%)was lower than that of the control group(11.67%),with statistical significance(P<0.05).Conclusion Compared with traditional surgery,TCAR for tonsillectomy and adenoidectomy in children with snoring can improve clinical efficacy,further improve ventilation capacity,reduce patient pain,shorten symptom relief time,improve sleep quality and living standards,and reduce the risk of postoperative complications.

Objective:To investigate the characteristics of gut microbiota in patients with type 2 diabetes (T2DM) complicated by nonalcoholic fatty liver disease (NAFLD).Methods:A total of 74 patients first diagnosed with T2DM at the Endocrinology Department of Peking Union Medical College Hospital from April 2021 to October 2023 were included. Among them, 28 patients had concurrent NAFLD while 46 patients did not. Additionally, 51 healthy controls were matched (HC group). Clinical laboratory parameters were collected, and 16S rRNA sequencing with fecal samples was conducted to compare the differences in gut microbiota across the groups.Results:Compared to the group with T2DM, patients with concurrent T2DM and NAFLD were younger, had higher level of insulin resistance as assessed by the homeostatic model assessment of insulin resistance, higher body mass index (BMI), and higher triglyceride levels. There was no difference in α-diversity across the three groups ( P>0.05), while there was a significant difference in β-diversity ( P=0.03). The Eubacterium coprostanoligenes, Fusicatenibacter, Parasutterella and Tyzzerella 3 were enriched in the group with concurrent T2DM and NAFLD as shown by the relative abundance, while the relative abundance of Flavonifractor was decreased in this group. Tyzzerella 3 abundance was positively correlated with triglyceride and albumin levels and negatively correlated with high-density lipoprotein cholesterol (HDL-C) levels. Conclusion:Patients with T2DM complicated by NAFLD exhibit dysbiosis in gut microbiota composition and specific genera abundance, with Flavonifractor identified as a potential protective factor for T2DM complicated by NAFLD.

Objective:To explore the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) from imaging perspective by analyzing voxel-based morphology (VBM) and functional connectivity (FC) in resting state functional magnetic resonance imaging (rs-fMRI).Methods:Thirty-five patients with NPSLE and 30 patients with non-NPSLE admitted to Department of Rheumatology and Immunology, Taizhou People's Hospital Affiliated to Nanjing Medical University from June 2020 to March 2023 were enrolled; 31 healthy subjects were included as healthy control group during the same period. All subjects completed routine MRI and rs-fMRI, laboratory tests (C3, C4, IgA, IgM and IgG levels), mini-mental state examination (MMSE), hospital anxiety and depression scale (HADS), and fatigue scale for motor and cognitive functions (FSMC). Whole brain gray matter volume in subjects of the 3 groups was analyzed by VBM method, and the brain regions enjoying significant differences in gray matter volume between the NPSLE group and non-NPSLE group were selected as regions of interest (ROIs) for whole brain FC analysis. Partial correlation method was used to analyze the correlations of imaging indexes in brain regions enjoying significant differences with clinical indexes and imaging scores between NPSLE group and non-NPSLE group. Efficacy of imaging indexes in brain regions enjoying significant difference in differentiating NPSLE from non-NPSLE was analyzed by receiver operating characteristic (ROC) curve.Results:(1) Covariance analysis among the 3 groups showed that the gray matter volume in the left inferior frontal gyrus of orbit, left superior frontal gyrus, right rectus gyrus, right transverse temporal gyrus, and right superior frontal gyrus was significantly different among the 3 groups ( P<0.001, FDR corrected); compared with the healthy control group, the NPSLE group had significantly reduced gray matter volume in the left inferior frontal gyrus of orbit, left superior frontal gyrus of orbit, right rectus gyrus, right transverse temporal gyrus, and right superior frontal gyrus ( P<0.001, FDR corrected); compared with the non-NPSLE group, the NPSLE group had significantly decreased gray matter volume in the left inferior frontal gyrus of orbit, right rectus gyrus, and right transverse temporal gyrus ( P<0.001, FDR corrected). (2) Whole brain FC analysis with brain regions enjoying significant differences as seed points showed that Fisher z-transformed FC (zFC) in the right transverse temporal gyrus and bilateral postcentral gyrus of the NPSLE group were significantly decreased ( P<0.001, FDR corrected). (3) Partial correlation analysis showed that, in the NPSLE group, zFC from the right transverse temporal gyrus to left posterior central gyrus was negatively correlated with disease course ( r=-0.390, P=0.027); gray matter volume in the right orbital superior frontal gyrus was negatively correlated with FSMC-cognitive ( r=-0.401, P=0.023); the gray matter volume in the right orbital superior frontal gyrus was negatively correlated with FSMC-motor ( r=-0.374, P=0.035). (4) ROC curve found that gray matter volume in the right rectus gyrus and zFC from the right transverse temporal gyrus to the right posterior central gyrus had relatively high efficacy in differentiating NPSLE from non-NPSLE, with AUC of 0.771 (95% CI: 0.658-0.885, P<0.001) and 0.794 (95% CI: 0.685-0.904, P<0.001), respectively. Conclusion:NPSLE patients have reduced gray matter volume in multiple brain regions (concentrating in the prefrontal limbic system); and reduced FC with some brain regions is noted; multiple indexes are correlated with clinical indexes.

Objective:To explore the causes of blood supply disorder of the pedicled rectus abdominis flap.Methods:Between January 2019 and May 2021, a cohort of 61 female patients, aged 25 to 70 years with a mean age of (46.9±2.1) years, underwent surgical repair for extensive thoracic wall defects at Hunan Province Cancer Hospital. These defects, resulting from thoracic wall tumor resection, were addressed using a combination of pedicled rectus abdominis myocutaneous flaps and free inferior abdominal artery perforator flaps. The patient cohort included 39 cases of locally advanced breast cancer, 12 cases of recurrent breast cancer, 6 cases of lobular cell sarcoma, and 4 cases of soft tissue sarcoma. The patients were divided into two groups according to the order of revascularization sequence of free inferior abdominal artery perforator flap: 31 cases in the group of anastomosing the artery first and then the accompanying vein (group A), and 30 cases in the group of anastomosing the vein first and then the artery (group B). The main reasons for the blood supply disorders of the pedicled rectus abdominis flap were analysed in the two groups.Results:In all 61 patients, the pedicled rectus abdominis myocutaneous flap showed immediate red and purple plaques and other blood supply disorders. Further anastomosis of the free inferior abdominal wall artery perforating the flap vessel tip was conducted to achieve pressurization. The vascular selection for the recipient area included the intrathoracic vessels in 26 cases, the thoracic acromion vessels in 15 cases, the thoracodorsal vessels in 9 cases, the anterior serratus branch of the thoracodorsal vessels in 7 cases, and the lateral thoracic arteries and veins in 4 cases. The flap length measured (29.1±0.6) cm, while the width of the skin island was (12.9±0.6) cm. The follow-up period was from 9 to 16 months, with a mean of 12.7 months.In the Group A, the flap blood supply was significantly relieved before further anastomosing the vein in 7 cases, and the flap blood supply returned to normal in the other 24 cases after further anastomosing the vein. In the Group B, the flap blood supply was significantly relieved before further anastomosing the artery in 27 cases, and the flap blood supply returned to normal in the other 3 cases after further anastomosing the artery.61 flaps survived completely, the shape of reconstructed chest wall was satisfactory, and there was no flap contracture and deformation; only linear scar was left in the donor area of the flap, and there was no significant effect on the function of the abdominal wall. The patients were followed-up for 9-16 months, with an average of 12.7 months.Conclusions:The main reason for the blood supply obstacle of the rectus abdominis flap is the venous return obstacle, in order to ensure the reliable blood supply of the flap, the venous return should be increased as a priority.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Type 2 Diabetes Mellitus(T2DM)is a chronic metabolic disease characterized by disorders of insulin and glucose.As a disease closely related to our daily diet,the molecular mechanism of its pathogenesis is still unclear.Sweet taste receptors are a kind of G protein-coupled receptors with 7 times transmembrane.Although the research on the pathogenesis of T2DM has been gradually deepened,there are few studies on the mechanism of sweet taste damage in the state of disease.Therefore,in-depth study of the pathological mechanism of T2DM sweet taste receptor damage is of great significance to further understand the molecular characteristics of sweet taste receptors and explore new targets of traditional Chinese medicine in the treatment of T2DM.In this paper,the biological characteristics of sweet taste receptors,signal transduction mechanism of sweet taste receptors,sweet taste receptors and T2DM,sweet taste receptors and"spleen is sweet"are reviewed in order to provide the latest opinions for the targeted prevention and treatment of this kind of diseases by traditional Chinese medicine and the elucidation of related pathological mechanism.

Objective:To evaluate the effect of metformin on ultraviolet A (UVA) -induced photoaging of an immortalized human keratinocytes cell line (HaCaT), and to explore its potential mechanisms.Methods:Cell counting kit 8 (CCK8) assay was performed to evaluate the effect of metformin at different concentrations (0 - 100 mmol/L) on the viability of HaCaT cells, and 10 mmol/L metformin was selected for subsequent experiments. Cultured HaCaT cells were divided into a blank control group (conventional culture), a metformin group (treated with culture medium containing 10 mmol/L metformin), a UVA irradiation group (conventional culture for 24 hours followed by 10 J/cm 2 UVA irradiation) and a metformin + UVA group (treated with culture medium containing 10 mmol/L metformin for 24 hours followed by 10 J/cm 2 UVA irradiation) ; UVA irradiation was performed at a dose of 10 J/cm 2 once a day for 3 consecutive days. After 4-day treatment, cells were collected, the β-galactosidase assay was performed to determine the proportion of senescent cells in each group, 2′, 7′-dichlorodihydrofluorescein diacetate assay to detect levels of intracellular reactive oxygen species (ROS), and the comet assay to detect DNA damage levels. Additionally, some HaCaT cells were divided into the blank control group, metformin group, 1.25 μmol/L dorsomorphin (an adenosine monophosphate-activated protein kinase [AMPK] inhibitor) + metformin group, and 2.5 μmol/L dorsomorphin + metformin group, and cells in the latter two groups were treated with 1.25 and 2.5 μmol/L dorsomorphin respectively for 2 hours, followed by the treatment with 10 mmol/L metformin for 24 hours. Western blot analysis was performed to determine the cellular localization and phosphorylation levels of nuclear factor-erythroid 2-related factor 2 (Nrf2). By using the small-interfering RNA (siRNA) -mediated silencing method, siRNA-Nrf2 was transfected into HaCaT cells to knock down Nrf2 expression (siRNA-Nrf2 group) ; 2.5 μmol/L dorsomorphin-treated HaCaT cells or Nrf2-knockdown HaCaT cells were treated with metformin and UVA irradiation (dorsomorphin + metformin + UVA group, siRNA-Nrf2 + metformin + UVA group, respectively), and the proportions of senescent cells were further calculated in each group. Statistical analysis was carried out by using one-way analysis of variance and two-way analysis of variance, and least significant difference (LSD) - t test was used for multiple comparisons. Results:Treatment with different concentrations of metformin for 24 hours could affect the viability of HaCaT cells to varying degrees ( F = 5 206.31, P < 0.001) ; there were no significant differences in the relative survival rates of HaCaT cells between the 10 - 20 mmol/L metformin groups and the control group (0 mmol/L metformin group, all P > 0.05), while the relative cell survival rates were significantly lower in the 25 - 100 mmol/L metformin groups than in the control group (all P < 0.05). After UVA irradiation, HaCaT cells shrank significantly and became narrow and elongated, and the intercellular spaces increased; the relative cell survival rate was significantly lower in the UVA irradiation group (76.13% ± 1.03%) than in the blank control group (100.00% ± 1.24%, LSD- t = 14.86, P < 0.001), but significantly higher in the metformin + UVA group (106.69% ± 2.45%) than in the UVA irradiation group (LSD- t = 11.55, P < 0.001). Moreover, the UVA irradiation group showed significantly increased proportions of senescent cells (45.14% ± 4.98%), intracellular ROS levels (144.61% ± 4.91%), and percentages of DNA in the tail (75.33% ± 1.77%) compared with the blank control group (23.84% ± 1.89%, 55.49% ± 1.57%, 1.88% ± 0.29%, respectively, all P < 0.001), while the metformin + UVA group showed significantly decreased proportions of senescent cells (24.26% ± 1.34%), intracellular ROS levels (58.62% ± 2.17%), percentages of DNA in the tail (15.83% ± 1.23%) compared with the UVA irradiation group (all P < 0.001). Western blot analysis showed that the Nrf2 expression in the cytoplasm was lower in the 10 mmol/L metformin group than in the blank control group, while the phosphorylated Nrf2 expression in the nuclei was higher in the 10 mmol/L metformin group than in the blank control group, suggesting that metformin could effectively induce the phosphorylation of Nrf2 and its nuclear translocation; both the pretreatment with 1.25 and 2.5 μmol/L dorsomorphin could significantly reduce the phosphorylation levels of AMPKα and Nrf2 induced by 10 mmol/L metformin. The proportions of senescent cells in the dorsomorphin + metformin + UVA group and the siRNA-Nrf2 + metformin + UVA group were 67.84% ± 2.74% and 65.94% ± 1.33%, respectively, which were significantly higher than those in the metformin + UVA group (37.76% ± 1.64%, t = 14.45, 13.34, respectively, both P < 0.001) . Conclusion:Metformin may inhibit UVA-induced photoaging of HaCaT cells by activating the AMPK/Nrf2 signaling pathway, scavenging ROS and reducing DNA damage.