OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

OBJECTIVE: To observe the clinical efficacy of Daoqi (directing qi flowing) acupuncture technique in Huangdi Neijing (Yellow Emperor's Inner Classic) for moderate-to-severe obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Sixty patients with moderate-to-severe OSAHS were randomly divided into a Daoqi acupuncture group (30 cases) and a conventional acupuncture group (30 cases, 1 case dropped out). In the Daoqi acupuncture group, Daoqi acupuncture technique in Huangdi Neijing was applied at Shanglianquan (Extra), Fengfu (GV16), and bilateral Lieque (LU7), Zhaohai (KI6); in the conventional acupuncture group, conventional acupuncture was applied at Shanglianquan (Extra), Fengfu (GV16), Yamen (GV15), and bilateral Lieque (LU7), Zhaohai (KI6), Zusanli (ST36), Fenglong (ST40). The treatment was adopted once every other day, 3 times a week, 4 weeks as one course and 3 courses were required totally in both groups. Before and after treatment, the polysomnography (PSG) indexes [apnea-hypopnea index (AHI), hypopnea index (HI), apnea index (AI), longest apnea duration, lowest nocturnal SaO₂ (LSaO₂)], and scores of Epworth sleepiness scale (ESS), Pittsburgh sleep quality index (PSQI), World Health Organization quality of life-BREF (WHOQOL-BREF) were observed, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, the AHI, HI, AI and longest apnea duration were reduced compared with those before treatment in the two groups (P<0.01), the LSaO₂ was increased in the Daoqi acupuncture group (P<0.01); in the Daoqi acupuncture group, the AHI, HI, AI and longest apnea duration were lower than those in the conventional acupuncture group (P<0.05), and the LSaO₂ was higher than that in the conventional acupuncture group (P<0.05). After treatment, the ESS and PSQI scores were decreased compared with those before treatment (P<0.01), while the WHOQOL-BREF scores were increased compared with those before treatment (P<0.01) in the two groups; in the Daoqi acupuncture group, the ESS and PSQI scores were lower than those in the conventional acupuncture group (P<0.05, P<0.01), and the WHOQOL-BREF score was higher than that in the conventional acupuncture group (P<0.05). The total effective rate was 93.3% (28/30) in the Daoqi acupuncture group, which was higher than 82.8% (24/29) in the conventional acupuncture group (P<0.01). CONCLUSION Daoqi acupuncture technique in Huangdi Neijing can effectively treat moderate-to-severe OSAHS patients, improve the clinical symptoms and quality of life, and has the advantages i.e. simpler acupoints selection and gentler stimulation.
Humans ; Sleep Apnea, Obstructive/physiopathology* ; Male ; Female ; Middle Aged ; Acupuncture Therapy ; Adult ; Acupuncture Points ; Treatment Outcome ; Aged ; Quality of Life

Background and Aims:Polycystic ovary syndrome(PCOS)is a common endocrine disorder among obese women,often accompanied by psychological issues such as anxiety and depression.Laparoscopic sleeve gastrectomy(LSG)is an effective treatment for obesity and its related metabolic conditions,and has shown clear benefits in improving weight and metabolic profiles in PCOS patients.However,the potential mechanisms by which psychological status may affect weight loss outcomes remain unclear.This study aimed to evaluate the psychological characteristics of obese patients with PCOS and explore their impact on postoperative weight loss outcomes,in order to provide evidence for individualized intervention strategies.Methods:Female obese patients scheduled for LSG between November 2020 and September 2022 were enrolled and divided into PCOS and non-PCOS groups.Standardized psychological scales were used to assess anxiety,depression,self-esteem,and eating behaviors.Weight loss outcomes were recorded at 6 and 12 months postoperatively.Propensity score matching was used to control for confounding factors such as age and body mass index(BMI),and correlation analysis was conducted to explore the relationship between psychological status and weight loss outcomes.Results:A total of 314 patients were included,with 130 cases(41.4％)in the PCOS group.Before matching,the PCOS group had significantly worse psychological indicators and lower weight loss outcomes compared to the non-PCOS group(all P＜0.05);after matching,these differences were no longer statistically significant(all P＞0.05).Emotional eating was positively correlated with 12-month weight loss outcomes in the PCOS group,while anxiety and internalized weight stigma were associated with weight loss outcomes in the non-PCOS group(P＜0.05).Additionally,among patients with moderate and extreme obesity,weight loss outcomes in the PCOS group were superior to those in the non-PCOS group(P＜0.05).BMI was negatively correlated with self-esteem,eating behaviors,and quality of life(all P＜0.05).Conclusion:Obese patients with PCOS exhibit notable psychological distress.However,after controlling for BMI and age,their psychological status and weight loss outcomes are comparable to those of non-PCOS patients.BMI may serve as an important confounding factor,and psychological factors may influence weight loss indirectly through eating behaviors.Preoperative psychological screening and intervention are recommended.

Objective:To investigate the short-term efficacy of robotic versus laparoscopic-assisted right hemicolectomy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 99 patients of right colon cancer who were admitted to Tianjin Medical University General Hospital from January 2020 to December 2023 were collected. There were 50 males and 49 females, aged 69(range, 26?89)years. Of the 99 patients, 41 patients undergoing robotic-assisted right hemicolectomy were divided into the robotic group, and 58 patients undergoing laparoscopic-assisted right hemicolectomy were divided into the lapa-roscopic group. Patients received robotic-assisted or laparoscopic-assisted right hemicolectomy operated by the same major surgeon. Observation indicators:(1) propensity score matching status and com-parison of clinical data of patients between the two groups after matching; (2) intraoperative and postoperative conditions.Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶1 nearest neighbor matching method. The caliper value was set as 0.1. Results:(1) Propensity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 99 patients, 82 patients were successfully matched, with 41 cases in each of the robotic group and the laparoscopic group. After propensity score matching, the elimination of history of abdominal operation confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After propensity score matching, the operation time of the robotic group was 215(range, 130?340)minutes, the volume of intraoperative blood loss was 50(range, 10?400)mL, the number of lymph node dissected was 21(range, 5?55), the number of intensive care unit stay was 15, time to postoperative first flatus was 3(range, 1?12)days, time to postoperative first food intake was 4(range, 2?14)days, duration of postoperative hospital stay was 8(range, 5?25)days. The above indicators of the laparoscopic group were 210(range, 140?370)minutes, 50(range, 5?150)mL, 19(range, 5?34),20, 3(range, 0?9)days, 5(range, 2?10)days, 8(range, 6?17)days, respectively. There was no significant difference in the above indicators between patients of the two groups ( Z=?0.94, ?1.87, ?1.32, χ2=1.25, Z=0.13, ?0.83, ?0.65, P>0.05). There was no patient converted to open operation in the robotic group, versus 1 patient converted to open operation in the laparoscopic group, showing no significant difference between patients of the two groups ( P>0.05). There were 6 cases in the robotic group and 4 cases in the laparoscopic group with complications, showing no significant difference between the two groups ( χ2=0.46, P>0.05). Both groups of patients achieved R 0 resection and had no readmission 30 days after surgery. The hospital expense was (11.0±1.8)×10 4 yuan of the robotic group, versus (9.0±1.7)×10 4 yuan of the laparoscopic group, showing a significant difference between the two groups ( t=?5.27, P<0.05). Conclusion:Robot-assisted right hemicolectomy is non inferior to laparoscopic-assisted right hemicolectomy in safety and efficacy, but with higher hospitalization costs.

Objective:To explore the effectiveness of the"full-chain"integrated medical and elderly care service model in addressing key issues in medical-nursing services such as weak medical support capacity and insufficient provision of community-and home-based medical-nursing services.Methods:The development pathway for the"full-chain"integrated medical-elderly care service standardization system,encompassing core components such as operational mechanisms,smart platforms,policy documents,and quality control systems was systematically outlined.Effectiveness based on dimensions including service coverage,quality improvement,talent development,and social benefits was evaluated.With standardization as the core driver,the'1234567'management model was innovatively implemented.Results:The model leveraged the downward allocation of high-quality resources from tertiary general hospitals to strengthen subdistrict community health service centers.By collaborating with subdistrict elderly-care service centers,it established"subdistrict medical-elderly care and wellness service centers".These centers enhanced the capabilities of"community-embedded elderly-care complexes",including community daytime care centers,established two-way referral channels between medical and elderly care services,aligned with healthcare demands to provide elderly individuals with reliable medical support.It reduced the burden on families and society,stimulated market vitality,boosted domestic demand,promoted the development of integrated medical-elderly care and wellness initiatives,thereby advancing the silver economy.With provincial government endorsement,the model had been applied to 203 communities across 37 counties by the end of 2024.Conclusion:The established"full-chain"integrated medical-elderly care service model facilitates regional high-quality development in integrated care by consolidating healthcare group resources and seamlessly connecting the service chain across hospitals,nursing homes,community institutions,and home-based settings,thereby creating a practical paradigm for comprehensive elderly care service delivery.

Objective Based on Network pharmacology to explore the mechanism of Compound Danshen Dripping Pills in treating Psycho-cardiological disease.Methods To obtain the validated targets of the complete formulation of Compound Danshen Dripping Pills,data were sourced from databases including China National Knowledge Infrastructure,Wanfang,VIP,and PubMed.Additionally,genes associated with Psycho-cardiological disease were retrieved from the Genecards database.Utilizing the Digital Intelligence Traditional Chinese Medicine Innovation Platform,network proximity was calculated for the obtained targets and genes.The potential targets of Compound Danshen Dripping Pills in the treatment of Psycho-cardiological disease conduct enrichment analysis,trace the source of medicinal materials and effective components absorbed into the blood.Results Obtained 192 targets for the Compound Danshen Dripping Pills,1137 genes for Psycho-cardiological disease,and the network proximity calculation showed a significant correlation between the two(Z-score=-6.5282).The enrichment analysis of the 95 potential targets predominantly reveals their association with several key pathways,including AGE-RAGE signaling in diabetic complications,Lipid and atherosclerosis,fluid shear stress and atherosclerosis,the HIF-1 signaling pathway,TNF signaling.The traceability analysis indicates that 80 targets are associated with three distinct medicinal materials,10 targets are linked to two medicinal materials,and 5 targets are connected to a single medicinal material.95 targets are mainly related to 17 effective blood components such as salvianolic acid B,tanshinone ⅡA,and salvianolic acid A.The top 16 key genes were obtained by sorting the targets based on the Betweenness values corresponding to the blood components.The enrichment analysis of the key gene indicated that the treatment of Psycho-cardiological disease with Compound Danshen Dripping Pills is associated with the positive regulation of smooth muscle cell proliferation and the hypoxia response.Additionally,it is linked to the AGE-RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis,the relaxin signaling pathway,lipid and atherosclerosis,and the TNF signaling pathway,etc.Conclusion The Compound Danshen Dripping Pills may improve Psycho-cardiological disease by regulating inflammatory response,oxidative stress,myocardial ischemia,neuroprotection,and neurotoxicity inhibition through components such as salvianolic acid B,tanshinone ⅡA,tanshinone Ⅰ,salvianolic acid A,protocatechuic acid,etc.

Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

Background and purpose:Melanoma is a highly invasive malignant tumor originating from melanocytes,which poses a great threat to human life and health around the world,and its morbidity and mortality have been rising continuously in recent years.Telomerase and autophagy play crucial roles in cell proliferation,survival and stress response.Telomerase maintains the replication ability of cells by prolonging telomeres at the ends of chromosomes,and autophagy,as a self-degradation mechanism of cells,can not only help cells remove damaged components to promote survival,but also induce cell death under certain conditions.In the tumor environment,they are often abnormally activated or out of balance,and participate in the occurrence and development of many cancers,including melanoma.This study investigated the roles of telomerase and autophagy in melanoma progression and evaluated the potential synergistic therapeutic effects of combined application of telomerase inhibitor BIBR1532 and autophagy inhibitor chloroquine(CQ)in melanoma treatment.Methods:Malignant melanoma cells A375 were treated with telomerase inhibitor BIBR1532.The cell viability was assessed using the cell counting kit-8(CCK-8)assay,and the cell apoptosis was detected using the Annexin Ⅴ/propidium iodide(PI)double staining method.Additionally,the expressions of autophagy-related proteins LC3-Ⅱand p62 were detected by Western blot,and the changes in autophagy flux were observed using dual-tagged adenovirus transfection technology.Based on these studies,BIBR1532 and the autophagy inhibitor CQ were further applied in combination to analyze cell proliferation,apoptotic rate,changes in mitochondrial membrane potential,and cell cycle distribution,and the cloning formation experiment was used to verify the cell's proliferative capacity,thereby comprehensively evaluating the efficacy of this combined treatment strategy.Results:Telomerase inhibitor BIBR1532 at a concentration of 50 μmol/L significantly inhibited the growth of malignant melanoma cells A375 and induced apoptosis.At the same concentration,BIBR1532 upregulated the expression of the autophagy-related protein LC3-Ⅱ in A375 cells,while downregulating the expression of p62 protein.By transducing A375 cells with a dual-tagged adenovirus,it was observed that autophagy flux was significantly enhanced after treatment with BIBR1532.Furthermore,the combined application of BIBR1532(50 μmol/L)and the autophagy inhibitor CQ(20 μmol/L)significantly promoted the death of A375 cells,induced apoptosis and destruction of mitochondrial membrane potential,caused cell cycle arrest at the G2/M phase,and significantly inhibited the cell's clonogenic ability.Conclusion:Telomerase inhibitor BIBR1532 not only inhibits the proliferation of malignant melanoma cells but also activates the autophagy process in these cells,and inhibition of the autophagy response by autophagy inhibitor CQ can enhance the sensitivity of malignant melanoma cells to telomerase inhibitor BIBR1532.

Objective: To investigate the trends in incidence and mortality of lung cancer in Huangpu District, Shanghai Municipality from 2002 to 2019, so as to provide the evidence for formulating lung cancer prevention and control measures. Methods: Data of lung cancer incidence and mortality among residents in Huangpu District from 2002 to 2019 were collected through the Shanghai Cancer Registration and Reporting Management System. The crude incidence and mortality of lung cancer was calculated, and standardized by the data from the Chinese Fifth National Population Census in 2000 (Chinese-standardized rate) and the Segi's world standard population in 1960 (world-standardized rate). The trends in incidence and mortality of lung cancer among residents by age and gender were evaluated using annual percent change (APC). Results: A total of 12 965 cases of lung cancer were reported in Huangpu District from 2002 to 2019, and the crude incidence rate was 80.66/105, the Chinese-standardized incidence rate was 34.54/105, and the world-standardized incidence rate was 31.30/105, all showing upward trends (APC=4.588%, 2.933% and 3.247%, all P<0.05). A total of 10 102 deaths of lung cancer were reported, and the crude mortality rate was 62.30/105, showing an upward trend (APC=0.959%, P<0.05); the Chinese-standardized mortality was 25.93/105, and the world-standardized mortality was 22.05/105, both showing downward trends (APC=-1.282% and -1.263%, both P<0.05). The crude incidence and mortality rates of lung cancer in males were higher than those in females (101.39/105 vs. 60.52/105, 85.45/105 vs. 39.87/105, both P<0.05). The crude incidence and mortality rates of lung cancer showed upward trends with age (both P<0.05), reaching their peaks in the age groups of 80-<85 years (341.37/105) and 85 years or above (355.97/105), respectively. Conclusions The incidence of lung cancer showed an upward trend, while the mortality showed a downward trend in Huangpu District from 2002 to 2019. Elderly men were the high-risk group for lung cancer incidence and mortality.

Objective: To construct a Family with sequence similarity 50 member A(FAM50A) gene knockout mouse insulinoma pancreatic β-cell line Beta-TC-6 using CRISPR/Cas9 gene editing technology and to prepare polyclonal antibodies specifically recognizing FAM50A. Methods: Two guide RNAs(sgRNAs) targeting the FAM50A gene were designed,and a recombinant plasmid expressing blue fluorescent protein(BFP) was constructed for gene knockout.The successfully constructed plasmid was transfected into Beta-TC-6 cells,and BFP-positive single cells were isolated for clonal expansion.The expanded monoclonal cell lines were genotyped by Sanger sequencing,and FAM50A protein expression was assessed by Western blot.Purified human recombinant FAM50A protein was used to immunize New Zealand rabbits for the preparation of a polyclonal antibody.The specificity of the prepared antibody was then validated using the successfully established FAM50A knockout cell line. Results: A monoclonal cell line with a successful knockout of the FAM50A gene was identified.Sanger sequencing confirmed base deletions at the target site.Western blot analysis showed a complete absence of FAM50A protein expression in this cell line.The prepared polyclonal antibody successfully recognized endogenous murine FAM50A protein in wild-type Beta-TC-6 cells and in hTERT-RPE1 cells overexpressing human FAM50A-GFP fusion protein,while no signal was detected in the FAM50A knockout cells. Conclusion This study successfully established a FAM50A gene knockout Beta-TC-6 cell model and generated a FAM50A polyclonal antibody,providing powerful tools for future research.