Objective: To analyze the association between drinking behaviors and anxiety symptoms, with the mediating role of insomnia symptoms among college freshmen, so as to provide a reference basis for reducing the occurrence of anxiety symptoms in college freshmen. Methods: From October to December 2021, 31 856 freshmen were selected by the purposive sampling method in 22 colleges across 11 provinces (Fujian, Jiangsu, Guangdong, Henan, Anhui, Hubei, Shanxi, Jiangxi, Shaanxi, Yunnan, Chongqing) in China. The Semi quantitative Food Frequency Questionnaire was used to investigate college freshmen drinking behaviors. The Depression Anxiety Stress Scale 21 and the Insomnia Severity Index were used to assess anxiety symptoms and insomnia symptoms in college freshmen. The generalized linear model was employed to analyze the association between drinking behaviors and anxiety symptoms in college freshmen, and the structural equation modeling was used to assess the mediating effect of insomnia symptoms on the association. Results: The detection rate of anxiety symptoms among college freshmen was 28.2%, the detection rates of the mild, moderate, severe and extremely severe were 6.6%, 15.9%, 3.2% and 2.6%, respectively. While 23.6% of college freshmen reported drinking in the past month, the rates were 39.8% among boys and 15.9% among girls. After adjusting for demographic variables (ethnicity, education, major, etc.) and confounding variables (self evaluation of learning burden, number of close friends, screen time, etc.), the results of generalized linear model analysis showed that beer consumption was associated with anxiety symptoms in college freshmen( β =0.09, 95% CI =0.04-0.14), girls( β =0.14, 95% CI =0.07-0.21) and those aged 19-20 years ( β =0.12, 95% CI =0.05-0.19)(all P <0.05). Red wine consumption was associated with anxiety symptoms in male students ( β =0.13, 95% CI =0.02-0.24, P <0.05). Alcohol and beer consumption were associated with insomnia in college freshmen[ β (95% CI ) =0.22(0.08-0.36),0.31(0.23-0.39),both P <0.01]. Insomnia symptoms partially mediated the association between drinking behaviors and anxiety symptoms among college freshmen with a mediating effect value of 0.05, accounting for 50.49% of the total effect. Conclusions Insomnia symptoms partially mediates the association between drinking behaviors and anxiety symptoms in college freshmen. Measures should be taken to simultaneously intervene in the drinking behaviors and insomnia symptoms of college freshmen to prevent the occurrence of their anxiety symptoms.

OBJECTIVE To establish a Chinese drug-related problem （DRP） classification system applicable to pharmacist-led pharmaceutical care in China， providing pharmacists with an effective and practical tool for pharmaceutical care. METHODS A multi-stage process was employed to construct the DRP classification system， including literature review and analysis， comparison of existing classification systems， refinement of classification items and framework development， two rounds of standard case validation， expert discussion， and system revision. The Fleiss′ kappa test was used to calculate the consistency coefficient κ， assessing the reliability of pharmacists participating in evaluating the classification system. An electronic questionnaire comprising six items was employed to evaluate the system’s applicability. RESULTS The constructed Chinese DRP classification system comprised six sections [problem（including potential problems）， DRP evaluation， cause （including possible causes of potential problems）， intervention， acceptance of intervention and DRP status]， with 24 primary codes and 96 secondary codes. In the first round of case validation， κ values exceeded 0.4 for all sections except “intervention” and “DRP status”. In the second round， κ values exceeded 0.4 for all sections. In the applicability evaluation of the classification system， positive ratings （“strongly agree” or “agree”） exceeded 85% for all items. Specifically， positive ratings for“the classification system can provide appropriate category selection”，“ the classification system is comprehensive”，“ the classification system is convenient to use” and “the classification system is highly satisfactory” exceeded 92%. CONCLUSIONS The Chinese DRP classification system developed demonstrates both high reliability and applicability， providing an effective and practical classification tool for pharmacists in China to conduct pharmaceutical care.

Objective:To investigate the effect of advanced glycation end products (AGEs) on ferroptosis in human retinal pigment epithelium (RPE) cell cultured in vitro. Methods:ARPE-19 cell lines were cultured in DMEM medium containing 10% fetal bovine serum (FBS), and the 3rd to 6th generations of cells were used for further study.Cell activity was detected by using the cell counting kit 8 after ARPE-19 were cultured with AGEs at 0, 50, 100, 200, 400 μg/ml for 48 hours.The cells were cultured with 200 μg/ml AGEs for 48 hours.Cell lipid peroxidation level was measured by Lipid Peroxidation Assay Kit (Bodipy 581/591 C11) combined with flow cytometry.The relative mRNA and protein expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were determined by quantitative real-time PCR (qRT-PCR) and Western blot.The morphology of mitochondria was observed by transmission electron microscope.Results:The activity of ARPE-19 cells decreased with increasing AGEs concentration, and the overall difference of ARPE-19 activity among 0, 50, 100, 200, 400 μg/ml AGEs groups was statistically significant ( F=6.21, P<0.01).The cell activity of ARPE-19 cells in 200 and 400 μg/ml AGEs groups was lower than that in control group (both P<0.05).Flow cytometry showed that the fluorescence intensity in AGEs group was 622.0±11.3, which was significantly higher than 487.7±12.8 in control group ( t=6.809, P=0.002).qRT-PCR showed that the mRNA and protein relative expression levels of SLC7A11 and GPX4 were lower in AGEs group than those in control group (mRNA: t=3.72, 7.14, both P<0.05; protein: t=6.20, 5.15, both P<0.05).Transmission electron microscopy showed that mitochondria in AGEs group shrank with significantly reduced volume, decreased mitochondrial cristae, and increased mitochondrial membrane density. Conclusions:AGEs can induce ferroptosis in ARPE-19 cultured in vitro.

Objective:To compare the effects of early orthodontic intervention and conventional sequential periodontal-orthodontic treatment to periodontal health in patients with stage Ⅳ periodontitis.Methods:A total of 30 patients with stage Ⅳ periodontitis, who underwent combined periodontal and orthodontic therapies at the Department of Periodontology, the Second Affiliated Hospital of Zhejiang University School of Medicine, from January 2018 to August 2024, were included. Patients who underwent early orthodontic intervention were initiated simultaneously or within one month after supragingival scaling and subgingival root planning ( n=15). While patients in control group accomplished supragingival scaling, subgingival root planning, and corresponding periodontal surgeries to achieve inflammation control before starting orthodontic treatment ( n=15). Periodontal parameters, including clinical attachment loss (CAL), probing depth (PD), and bleeding on probing (+) % [BOP (+) %], were measured at baseline, one year after orthodontic treatment, and at the end of combined periodontal-orthodontic therapy respectively. Improvements in periodontal parameters and differences in tooth loss between the two groups were compared. Results:After receiving combined periodontal-orthodontic treatment, the CAL of the early orthodontic intervention group significantly decreased from (4.39±0.90) mm before treatment to (2.41±0.35) mm at the end of treatment ( t=7.92, P<0.001). Similarly, the PD significantly reduced from (4.20±1.04) mm before treatment to (2.20±0.38) mm at the end of treatment ( t=7.01, P<0.001). The BOP(+)% also showed a significant improvement, decreasing from 89.29% (68.00%, 100.00%) before treatment to 13.04% (7.14%, 17.86%) at the end of treatment ( Z=-3.41, P<0.001). There were no statistically significant differences between the early orthodontic intervention group and control group in terms of baseline mean CAL, mean PD, and BOP(+)% ( t=1.30, P=0.205; t=1.28, P=0.212; Z=0.58, P=0.559). Furthermore, the improvements in CAL and PD between the two groups were not significantly different compared to baseline ( Z=-1.10, P=0.272; Z=-0.93, P=0.351). However, the number of missing teeth was significantly lower in the early orthodontic intervention group than in the control group (χ2=3.96, P=0.047). The duration of combined periodontal-orthodontic treatment in the early orthodontic intervention group was [33.13 (23.37, 36.20) months], which was significantly shorter than that in the control group [37.47 (32.33, 50.90) months] ( Z=2.07, P=0.037). Conclusions:Both early orthodontic intervention and conventional periodontal-orthodontic treatment significantly improved CAL, PD, and BOP(+)% in stage Ⅳ periodontitis patients. Early orthodontic intervention contributed to the preservation of natural teeth and shortened the treatment duration of stage Ⅳ periodontitis.

Objective To investigate the protective effects of paeonol(PAE)on autophagy in human neuroblastoma cells(SH-SY5Y)induced by overexpression of α-synuclein(α-Syn),and to explore its related mechanism.Methods SH-SY5Y cells served as control group,while those induced with A53T-α-Syn mutation were used as model group.Additional groups included PAE(150 μg/ml)group,3-MA(1 mmol/L)group,and PAE(150 μg/ml)+3-MA(1 mmol/L)group.Cell viability was assessed using CCK-8 method,cell morphology was observed under an optical microscope,and protein expressions of α-Syn,LC3-Ⅱ,p62,Beclin-1,phosphorylated c-Jun N-terminal kinase(p-JNK),and p-Bcl-2 were determined by Western blotting.Results Compared with control group,model control exhibited decreased cell survival(P＜0.01),increased α-Syn expression(P＜0.001),reduced expression of autophagy-related proteins LC3-Ⅱ and Beclin-1(P＜0.01,P＜0.05),elevated autophagy substrate protein p62(P＜0.05),and decreased expression of autophagy pathway-related proteins p-JNK and Bcl-2(P＜0.05,P＜0.01).Compared with model group,PAE group showed increased cell survival(P＜0.01),decreased α-Syn and p62 protein expression(P＜0.01,P＜0.05),and increased expression of LC3-Ⅱ,Beclin-1,p-JNK and Bcl-2(P＜0.05).Compared with PAE group,3-MA+PAE group demonstrated increased α-Syn expression(P＜0.05).Conclusions PAE could attenuate the injury of SH-SY5Y cells induced by A53T-α-Syn and eliminate over-expressed α-Syn by activating autophagy pathway,which may be associated with the upregulation of JNK/Bcl-2 mediated autophagy pathway.

Objective To investigate the relationship between tooth loss and the occurrence of esophageal cancer in a natural village in Wenfeng District, Anyang City, Henan Province. Methods A prospective cohort study was conducted to observe the occurrence of tooth loss and esophageal cancer among the asymptomatic residents of the natural village for 16 years from January 2008 to July 2024. Data were analyzed by chi-square test, binary logistic regression, and restricted cubic spline. Results Among the total population of 711 cases, 136 cases were lost to follow-up and 575 cases were included in the final statistics, including 45 cases with esophageal cancer. Significant statistical difference was found between esophageal cancer patients with and without tooth loss (P<0.05). Logistic regression analysis showed that tooth loss was associated with the occurrence of esophageal cancer (OR=3.977, 95%CI: 1.543-10.255). After the adjustment for confounders, tooth loss remained significantly associated with the occurrence of esophageal cancer (OR=3.038, 95%CI: 1.035-8.914). A nonlinear dose-response relationship was observed between the number of teeth lost and the incidence of esophageal cancer. When the number of teeth lost was less than 12, the risk of esophageal cancer increased with the number of teeth lost. When more than 12 teeth were lost, the risk of esophageal cancer decreased as the number of teeth lost increased. Conclusion Tooth loss is a risk factor for the occurrence of esophageal cancer in this natural village. When the number of teeth lost is less than 12, the risk of esophageal cancer increases with the number of teeth lost.

Background: Influenza A viruses (IAVs) are the major pathogens associated with respiratory infections which can result in extensive pathological damage in lungs and serious complications. Isorhamnetin, an abundant natural flavonoid in fruits and medicinal plants, has recently been shown to have strong antioxidative, anti-inflammatory, and antiviral effects. Objective: This study investigated the pharmacological effects of isorhamnetin on viral pneumonia and explored the underlying mechanisms by in vivo and in vitro experiments. Materials and methods: In the present study, the protective effect of isorhamnetin against IAV was evaluated by the cytopathogenic effect assay, cell counting kit-8 assay, real-time polymerase chain reaction, and immunofluorescence assay in vitro. Then the pathological damage associated with pneumonia was examined by calculating the pulmonary index and performing micro-CT and hematoxylin-eosin staining in vivo. Thereafter, the related protein or gene levels of factors in the mitogen-activated protein kinase (MAPK) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathways were determined by Western blot and immunofluorescence staining. Results: Isorhamnetin exerted significant anti-influenza effects and inhibited the expression of viral RNA in A549 cells, counteracting oxidative stress and apoptosis by suppressing the production of reactive oxygen species and caspase-3. The in vivo experiment results showed that isorhamnetin (20 and 40 mg/kg) caused a significant decrease in the pulmonary index, ameliorated pathological damage in the lung tissue, decreased viral load and NA activity, and reduced cytokines and nuclear factors. Furthermore, isorhamnetin could counteract the B cell lymphoma-2/B cell lymphoma-2–associated X protein (Bax) imbalance induced by PR8, suppress activation of the MAPK pathway, and upregulate the expression of Nrf2 and HO-1. Conclusions: Isorhamnetin can protect against viral pneumonia by activating the Nrf2/HO-1 pathway and suppressing the MAPK path-way. This study deciphers the pharmacological mechanism of isorhamnetin in alleviating pathological damage in viral pneumonia and provides rationale for the application of isorhamnetin in influenza treatment.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Activating transcription factor 5 (ATF5) is a member of the activating transcription factor/cyclic adenosine monophosphate response element binding protein (ATF/CREB) family. As a stress-induced transcription factor, ATF5 plays a crucial role in cellular inflammatory stress responses. Under cellular inflammatory stress conditions, ATF5 maintains cell homeostasis and survival by regulating key genes in the mitochondrial unfolded protein response (UPR^mt) and endoplasmic reticulum stress (ERS). As a key regulator in UPR^mt, ATF5 senses mitochondrial stress and translocate to the nucleus to activate the transcription of UPR^mt-related genes, thereby promoting mitochondrial function recovery. Meanwhile, in ERS, ATF5 maintains endoplasmic reticulum homeostasis by regulating the expression of genes related to protein folding, degradation, and apoptosis, determining cell survival or death. ATF5 plays a vital role in various cellular inflammatory stress responses. In infectious inflammation, ATF5 plays an important role in alleviating neuroinflammation and maintaining intestinal barrier function by regulating UPR^mt. In inflammation related to degenerative diseases, ATF5 improves intervertebral disc degeneration and delays the progression of osteoarthritis by regulating UPR^mt. In metabolic inflammation such as diabetes and obesity, ATF5 regulates UPR^mt and ERS to maintain the function of pancreatic β-cells, controlling their survival or inducing apoptosis, thus influencing the progression of diabetes. ATF5 protects mitochondria in the kidneys, adipose tissue, and pancreas, slows the progression of diabetic nephropathy, and improves insulin sensitivity. Furthermore, in immune-related inflammation, ATF5 alleviates glomerulonephritis and promotes tissue repair by enhancing immune tolerance in dendritic cells. In summary, ATF5, as a key regulator in cellular inflammatory stress responses, maintains cell homeostasis through regulating UPR^mt and ERS and determines cell fate. Its critical regulatory role in cellular inflammatory stress responses makes ATF5 a potential clinical therapeutic target. This article summarizes the structural features and translational regulatory mechanisms of ATF5, focusing on its role in cellular inflammatory stress responses, particularly its regulatory mechanisms in UPR^mt and ERS, aiming to provide a theoretical basis for understanding ATF5's role in cell and organ protection and to offer new insights into the treatment of related inflammatory diseases.
Humans ; Endoplasmic Reticulum Stress ; Inflammation/metabolism* ; Activating Transcription Factors/metabolism* ; Unfolded Protein Response ; Mitochondria/metabolism* ; Apoptosis ; Animals