OBJECTIVE:To investigate the effects of quercetin on human lung cancer NCI-H1395 cell apoptosis. METHODS:CCK-8 was used to detect the effects of 0-200 μmol/L quercetin on human lung cancer NCI-H1395 cell proliferation after treated for 12,24 and 48 h. Hochest33258 staining and flow cytometry were used to detect the effects of 0,20,50,100 μmol/L quercetin on NCI-H1395 cell apoptosis after treated for 24 h. The effects of 100 μmol/L quercetin on NCI-H1395 cell apoptosis was investi-gated after treated with Caspase-8,Caspase-9,Caspase-3 inhibitor. RESULTS:Quercetin could inhibit NCI-H1395 cell prolifera-tion in dose and time-dependent manner. 20,50,100 μmol/L quercetin could induce the apoptosis of NCI-H1395 cell,and apoptot-ic rates were (18.6 ± 4.1)%,(39.1 ± 4.5)% and (58.2 ± 3.5)%. Caspase-8 and Caspase-3 activation inhibition could obviously weaken the inhibitory effects of quercetin on cell(P<0.05). CONCLUSIONS:Quercetin can inhibit NCI-H1395 cell proliferation and induce cell apoptosis,which is related to the external way of cell apoptosis through activating Caspase-8 and Caspase-3.

Objective The rate of post -operative complications has been increased with the changes in patients' age,prolonged duration, more severe and diffused lesions, and more patients with complications in recent years. We try to identify the risk factors associated with prolonged stay in the intensive care unit ( ICU ) after coronary artery bypass graft surgery (CABG). Methods 1623 patients who received CABG surgery in Beijing Anzhen Hospital Between June 1, 2006 and December 31,2007 were divided into two groups based on their stay duration in the ICU. Prolonged stay in ICU was defined as 5days or more. Univariate and multivariate analysis ( logistic regression) were used to identify the risk factors. The discrimination and calibration of the result were tested after the risk factors were determined. Results Fifty one patients had prolonged ICU stay, accounting for 3.14% of total cases. Multivariate logistic analysis showed that the age of patients, peripheral vascular diseases, critical status before operation, LVEF, operative status, mitral regurgitation, postoperative respiratory failure,postoperative renal failure, secondary thoracotomy for postoperative bleeding were associated risk factors. Conclusion Prolonged ICU stay after CABG surgery can be predicted based on the above factors. For patients with these risk factors, more pre-and postoperative care strategies are needed.

Objective To investigate the correlation of human epididymis protein 4(HE4)with proteinuria in patients with type 2 diabetes mellitus(T2DM).Methods A total of 147 T2DM patients from January 2020 to July 2023 in Jiujiang NO.l People's Hospital were enrolled in observation group.According to the severity of proteinuria,observation group was divided into three groups:Normal albuminuria group(101 cases),microalbuminuria group(25 cases),and massive albuminuria group(21 cases).50 healthy examinees with gender and age matching during the same period were selected as control group.HE4 levels and clinical indicators in each group were compared and analyzed.Correlation between HE4 and proteinuria was analyzed by using univariate and multivariate linear regression.Results The correlation network diagram reveals that HE4 functions was a pivotal node linking serum albumin,urinary microalbumin,urinary microalbumin-to-creatinine ratio(UACR),and renal function biomarkers.Compared to control group,HE4 levels significantly elevated in observation group(P＜0.01).Both univariate and multivariate linear regression analysis demonstrate a positive correlation between HE4 and UACR.Logistic regression analysis shew that after adjusting for confounding factors including age,gender,estimated glomerular filtration rate(eGFR),albumin(ALB),blood urea nitrogen(BUN),serum creatinine(SCr),uric acid(UA),lactate dehydrogenase(LDH)etc.elevated HE4 levels was a risk factor for proteinuria(OR=1.110,95％CI:1.005-1.226).Conclusion Elevated HE4 levels in patients with T2DM is positivly correlated with UACR.Increase its level increases the risk of proteinuria in T2DM patients.

-Methyladenosine (mA) modification is the most pervasive modification of human mRNA molecules. It is reversible regulation of mA modification methyltransferase, demethylase and proteins that preferentially recognize mA modification as "writers", "erasers" and "readers", respectively. Altered expression levels of the mA modification key regulators substantially affect their function, leading to significant phenotype changes in the cell and organism. Recent studies have proved that the mA modification plays significant roles in regulation of metabolism, stem cell self-renewal, and metastasis in a variety of human cancers. In this review, we describe the potential roles of mA modification in human cancers and summarize their underlying molecular mechanisms. Moreover, we will highlight potential therapeutic approaches by targeting the key mA modification regulators for cancer drug development.

ObjectiveTo analyze the epidemiological characteristics of senile dementia death in Jing’an District from 2016 to 2020， as well as the trends of mortality， standardized mortality， years of life lost （YLL） due to early death， years lived with disability （YLD）， and disability-adjusted life year （DALY）， and to provide scientific basis for the prevention and control of senile dementia. MethodsThe distribution of senile dementia in terms of gender， age， marital status and education level was investigated in the senile dementia death cases from 2016 to 2020 in Jing’an District. The YLL， YLD， DALY and their rates of the residents of Jing’an District from 2016 to 2020 were calculated by using Global Burden of Disease （GBD 2019） research method and results in combination with the corresponding population data. ResultsCompared to those without dementia， deaths with dementia were more likely to be female， more likely to be over 80 years old， less likely to be married， and more likely to have education level under middle school. Among the deaths with dementia， only 27.70% of the primary cause of death was dementia， and the other main causes were cerebrovascular disease， coronary heart disease and diabetes mellitus， which accounted for 25.54%， 17.81% and 7.28%， respectively. There was a significant gender difference in the burden of disease on senile dementia in Jing’an District. Mortality， standardized mortality， YLL， YLD and DALY rates of females were higher than those of males. The burden of disease on senile dementia increased with age. The change trend of mortality and YLL rate from 2016 to 2020 was not statistically significant， while the YLD rate and DALY rate showed an upward trend， which was statistically significant. ConclusionAs the life span of residents in Jing’an District increases and the population aging deepens， the burden of disease on senile dementia is still heavy. This requires extensive attention of the whole society， and active exploration of prevention and control strategies and measures for senile dementia， so as to improve the life quality of patients and reduce the burden of disease.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Background Diabetes mellitus is a major public health issue at present. Previous studies have shown that ambient air pollution is a risk factor for diabetes. Objective This study aims to explore the acute effects of ambient air pollution on diabetes related death in Shanghai Jing’an District. Methods Daily air pollution data, meteorological data, and diabetes related mortality data in 2013−2019 in Shanghai Jing’an District were collected. A generalized additive model (GAM) was established to conduct time-series analysis on the short-term effect of ambient air pollution on diabetes related mortality, and gender- and age-stratified analysis on susceptibility of various groups to ambient air pollution exposures. Results For every 10 μg·m⁻³ increase of the concentrations of PM_2.5, PM₁₀, SO₂, and NO₂, the diabetes related mortality increased by 2.47% (95%CI: 1.56%−3.38%), 2.02% (95%CI: 1.29%−2.75%), 5.75% (95%CI: 2.99%−8.58%), and 3.93% (95%CI: 2.49%−5.39%) at lag05 respectively (P<0.05). In the stratified analysis, exposures to increased concentrations of PM_2.5, PM₁₀, SO₂, and NO₂ raised the mortality risks from diabetes in male, female, and ≥65 years oldgroups (P<0.05). However, the differences in mortality risks from diabetes due to air pollution within gender and age groups were statistically insignificant. Conclusion In Shanghai Jing'an District, the elevated levels of ambient air pollutants, including PM_2.5, PM₁₀, SO₂, and NO₂, are significantly associated with the increase of diabetes related mortality, and there are lag effects and cumulative effects. The ≥65 years olds are more susceptible to the impact of air pollution on diabetes related deaths.

Hepatotoxicity is a common side effect for patients treated with gefitinib, but the related pathogenesis is unclear and lacks effective predictor and management strategies. A multi-omics approach integrating pharmacometabolomics, pharmacokinetics and pharmacogenomics was employed in non-small cell lung cancer patients to identify the effective predictor for gefitinib-induced hepatotoxicity and explore optional therapy substitution. Here, we found that patients with rs4946935 AA, located in Forkhead Box O3 (FOXO3) which is a well-known autophagic regulator, had a higher risk of hepatotoxicity than those with the GA or GG variant (OR = 18.020, 95%CI = 2.473 to 459.1784, P = 0.018) in a gefitinib-concentration dependent pattern. Furthermore, functional experiments identified that rs4946935_A impaired the expression of FOXO3 by inhibiting the promotor activity, increasing the threshold of autophagy initiation and inhibiting the autophagic activity which contributed to gefitinib-induced liver injury. In contrast, erlotinib-induced liver injury was independent on the variant and expression levels of FOXO3. This study reveals that FOXO3 mutation, leading to autophagic imbalance, plays important role in gefitinib-induced hepatotoxicity, especially for patients with high concentration of gefitinib. In conclusion, FOXO3 mutation is an effective predictor and erlotinib might be an appropriately and well-tolerated treatment option for patients carrying rs4946935 AA.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.