Therapeutic resistance in cancer is responsible for numerous cancer deaths in clinical practice. While target mutations are well recognized as the basis of genetic resistance to targeted therapy, nontarget mutation resistance (or nongenetic resistance) remains poorly characterized. Despite its complex and unintegrated mechanisms in the literature, nongenetic resistance is considered from our perspective to be a collective response of innate or acquired resistant subpopulations in heterogeneous tumors to therapy. These subpopulations, e.g., cancer stem-like cells, cancer cells with epithelial-to-mesenchymal transition, and drug-tolerant persisters, are protected by their resistance traits at cellular and molecular levels. This review summarizes recent advances in the research on resistant populations and their resistance traits. NOTCH signaling, as a central regulator of nongenetic resistance, is discussed with a special focus on its canonical maintenance of resistant cancer cells and noncanonical regulation of their resistance traits. This novel view of canonical and noncanonical NOTCH signaling pathways is translated into our proposal of reshaping therapeutic strategies targeting NOTCH signaling in resistant cancer cells. We hope that this review will lead researchers to study the canonical and noncanonical arms of NOTCH signaling as an integrated resistant mechanism, thus promoting the development of innovative therapeutic strategies.
Neoplasms/metabolism* ; Receptors, Notch/metabolism* ; Disease Resistance/physiology* ; Signal Transduction/physiology* ; Humans ; Drug Resistance, Neoplasm/physiology* ; Molecular Targeted Therapy/methods*

Purpose/Significance To apply the 5G ward round robot platform in primary hospitals,so as to effectively improve the treatment capability and management service level of patients with critical and severe diseases.Method/Process Based on technologies such as 5 G,internet of things(IoT)and robotics,the researchers build and deploy a 5 G ward round robot platform and collaborate with domestic experts to provide mobile ward round,remote consultation,intensive care,health education and other services for patients.Re-sult/Conclusion Real time sharing of patient clinical data and efficient collaboration in the diagnosis and treatment process can be a-chieved,multi-mode,accurate and standardized remote ward round and treatment guidance can be carried out according to patients'conditions.

Objective To analyze the epidemiological characteristics of population-based cohort of patients with the comorbidity of cardiovascular and cerebrovascular diseases and type 2 diabetes in Lingnan area,and to study the related influencing factors in the onset and progression of the disease. Methods A retrospective cohort study was used to collect data from people who underwent physical examination in the Eleventh People's Hospital of Guangzhou from May 2022 to December 2023. Data mainly included questionnaire surveys,physical examinations,and laboratory testing indicators. The 2022 was defined as the baseline to statistically analyze the occurrence and development of the comorbidity of cardiovascular and cerebrovascular diseases and type 2 diabetes in this population,and to analyze the related influencing factors of comorbidity and distribution of traditional Chinese medicine constitution in comorbidity population. Results Finally,a total of 26498 subjects were included,from which there were 359 patients with the comorbidity of cardiovascular and cerebrovascular diseases and type 2 diabetes (comorbidity group),accounting for 1.4％ of the total. Among them,290 were male,accounting for 80.8％,which is much higher than female. The mean age was(61.6±9.5)years old,which was significantly higher than that of the non-comorbidity group. The cases of comorbidity group were mainly concentrated in the age group of 45-75 years old,and no cases were found in people under 35 years old. There were 293 patients with the comorbidity of ischemic cardiovascular disease and type 2 diabetes,whose proportion (81.6％) is much higher than that of other types. Significant differences between comorbidity group and non-comorbidity group were found in terms of gender,age,age distribution,height,body mass,body mass index (BMI),smoking,alcohol consumption,marital status,exercise,and dampness syndrome (P<0.05). About 1.0％ of population at the baselined converted from non-comorbidities or single disease to comorbidities. The proportion of newly diagnosed patients with the comorbidity of ischemic cardiovascular disease and type 2 diabetes is the highest,up to 68.9％. BMI overweight or obesity,large waist circumference,smoking,dampness syndrome and exercise were the risk factors affecting the comorbidity of cardiovascular and cerebrovascular diseases and type 2 diabetes. A total of 264 cases of comorbidity group had finished evaluation of traditional Chinese medicine body constitutions. The proportion of balanced constitution was the highest (31.1％),followed by dampness-heat constitution (18.2％),yang-deficiency constitution (13.3％) and phlegm-dampness constitution (11.7％). Conclusion The incidence of the comorbidity of cardiovascular and cerebrovascular diseases and type 2 diabetes is high in Lingnan area,which may be related to dampness constitution,BMI overweight or obesity,large waist circumference,smoking,dampness syndrome and lack of exercise.

Oral submucous fibrosis(OSF)is a chronic and inflammatory mucosal disease caused by betel quid chewing,which belongs to oral potentially malignant disorders.Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development.The epithelium,which is the first line of defense against the external environment,can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment.However,the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear.In this study,we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes.MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts,where it promoted cell secretion,contraction,migration and fibrogenic marker(α-SMA and collagen type I)expression.The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1(TGFBR1)through the E3 ubiquitination ligase WWP1,thus facilitating downstream TGF-β pathway signaling.Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes.Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts.In conclusion,we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway,which provided a new perspective and strategy for the diagnosis and treatment of OSF.

Oral submucous fibrosis(OSF)is a chronic and inflammatory mucosal disease caused by betel quid chewing,which belongs to oral potentially malignant disorders.Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development.The epithelium,which is the first line of defense against the external environment,can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment.However,the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear.In this study,we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes.MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts,where it promoted cell secretion,contraction,migration and fibrogenic marker(α-SMA and collagen type I)expression.The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1(TGFBR1)through the E3 ubiquitination ligase WWP1,thus facilitating downstream TGF-β pathway signaling.Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes.Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts.In conclusion,we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway,which provided a new perspective and strategy for the diagnosis and treatment of OSF.

【Objective】 To investigate the effect of multiple apheresis platelet donation on platelet indexes and aggregation function in platelet donors, and to analyze the relationship between platelet indexes and their relationship with platelet aggregation rate. 【Methods】 A total of 83 platelet donors were randomly selected from Foshan Central Blood Station from September 2021 to October 2022, and were divided into control group (n= 9, first-time platelet donors or donors with the time interval from the last platelet donation >1 year) and study group (n= 74, repeat platelet donors or donors with the time interval from the last platelet donation ≤ 1 year) according to the times of blood donation. The study group was divided into 4 subgroups: 2-5 times group, 6-10 times group, 11-15 times group and 16 times group. The platelet count(Plt), platelet distribution width (PDW), mean platelet volume (MPV), large platelet ratio (P-LCR), and maximum platelet aggregation rate (MAR) before donation in each group were detected and analyzed. 【Results】 There were no significant differences in Plt, MPV, PDW, P-LCR and MAR between the subgroups and the control group (P>0.05), and there were no significant differences in Plt, MPV, PDW, P-LCR and MAR between each subgroup (P>0.05) .There was a positive correlation between Plt and MAR in blood donors (P<0.05), and the correlation coefficient was 0.445. MPV, PDW and P-LCR were negatively correlated with MAR (P<0.05), and the correlation coefficients were -0.282, -0.233 and -0.217, respectively. Plt was negatively correlated with MPV, PDW and P-LCR (P < 0. 05), and the correlation coefficients were -0.399, -0.307 and -0.339, respectively. MPV, PDW and P-LCR are positively correlated with each other. The correlation coefficient between MPV and PDW was 0.792, that between MPV and P-LCR was 0.863, and tthat between PDW and P-LCR was 0.817. 【Conclusion】 There was no significant effect of multiple platelet donations on Plt, PDW, MPV, P-LCR and MAR in blood donors. Plt has the most significant impact on MAR among platelet indexes of platelet donors.

Objective:To investigate regional distribution and clinicopathological features of Epstein-Barr virus associated gastric cancer (EBVaGC).Methods:Epstein-Barr virus encoded RNA (EBER)was detected in 4 081 cases of gastric adenocarcinoma in Cancer Hospital, Chinese Academy of Medical Sciences by using in situ hybridization. EBVaGCs were identified and their proportions in different provinces, autonomous regions and municipalities were compared. The correlation between EBVaGC and clinicopathological features was also analyzed.Results:A total of 3.0% (123/4 081) patients with gastric adenocarcinoma are EBVaGCs. Among the areas with cases more than 90, the highest proportion of EBVaGC was found in Jilin province, accounting for 7.6%, and then followed by 5.4% in Liaoning province, 4.1% in Anhui province, 3.9% in Beijing, 3.7% in Inner Mongolia Autonomous Region, 3.4% in Shanxi province, 3.0% in Heilongjiang province, 2.1% in Shandong province, 1.6% in Hebei province, and no EBVaGC was found in Henan province. EBVaGC proportions are significantly different in these provinces, autonomous regions and municipalities ( P<0.05). Multivariate analysis of logistic regression revealed that gender ( OR=2.231, 95% CI: 1.290~3.858), WHO classification ( OR=2.338, 95% CI: 2.051~2.664) and N stage ( OR=0.420, 95% CI: 0.284~0.621) were independent impact factors for EBVaGC. The proportion of EBVaGC was higher in males, gastric carcinomas accompanied with lymphoid stroma and patients without lymph node metastasis. Conclusions:The proportion of EBVaGC in gastric adenocarcinoma displays area distribution disparity in China. The gender, WHO classification and N stage are closely associated with EBVaGC.

Objective:To investigate regional distribution and clinicopathological features of Epstein-Barr virus associated gastric cancer (EBVaGC).Methods:Epstein-Barr virus encoded RNA (EBER)was detected in 4 081 cases of gastric adenocarcinoma in Cancer Hospital, Chinese Academy of Medical Sciences by using in situ hybridization. EBVaGCs were identified and their proportions in different provinces, autonomous regions and municipalities were compared. The correlation between EBVaGC and clinicopathological features was also analyzed.Results:A total of 3.0% (123/4 081) patients with gastric adenocarcinoma are EBVaGCs. Among the areas with cases more than 90, the highest proportion of EBVaGC was found in Jilin province, accounting for 7.6%, and then followed by 5.4% in Liaoning province, 4.1% in Anhui province, 3.9% in Beijing, 3.7% in Inner Mongolia Autonomous Region, 3.4% in Shanxi province, 3.0% in Heilongjiang province, 2.1% in Shandong province, 1.6% in Hebei province, and no EBVaGC was found in Henan province. EBVaGC proportions are significantly different in these provinces, autonomous regions and municipalities ( P<0.05). Multivariate analysis of logistic regression revealed that gender ( OR=2.231, 95% CI: 1.290~3.858), WHO classification ( OR=2.338, 95% CI: 2.051~2.664) and N stage ( OR=0.420, 95% CI: 0.284~0.621) were independent impact factors for EBVaGC. The proportion of EBVaGC was higher in males, gastric carcinomas accompanied with lymphoid stroma and patients without lymph node metastasis. Conclusions:The proportion of EBVaGC in gastric adenocarcinoma displays area distribution disparity in China. The gender, WHO classification and N stage are closely associated with EBVaGC.

OBJECTIVETo evaluate the semen quality of the donors.

METHODSThe semen parameters of the primary samples of 512 donors were examined following the World Health Organization (WHO) guide and computer-aided sperm analysis (CASA, product by Harmilton Thorne) system.

RESULTSOf the 246 (246/512, 48%) donors with potential fertility, only 146 (146/512, 28.5%) came up to the semen standard set by the Chinese Ministry of Health, while 266 (266/512, 52%) were below the WHO reference values of semen parameters.

CONCLUSIONRepeat semen analyses may increase the success rate in screening semen donors. The semen quality of the donors suggests that it is necessary to pay more attention to male reproductive health.

Adult ; Humans ; Image Processing, Computer-Assisted ; Male ; Mass Screening ; Middle Aged ; Reference Values ; Semen ; physiology ; Sperm Banks ; Sperm Count ; Sperm Motility ; Tissue Donors