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.

Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

Objective To investigate the relationship between the levels of Versican(VCAN)and Cyclin D1(CCND1)in peripheral blood and the progression and prognosis of multiple myeloma(MM).Methods A total of 121 patients with MM(MM group)and 109 healthy volunteers(control group)were selected and admitted to the Department of Hematology of Suzhou Municipal Hospital from January 2018 to May 2022.According to the International Staging System(ISS),the patients with MM were divided into a stage I group(n=46),a stage II group(n=41),and a stage III group(n=34).Real time fluorescence quantitative PCR(RT-PCR)was used to detect the expression levels of VCAN mRNA and CCND1 mRNA in peripheral blood,the patients were followed up for 24 months after discharge to make statistics on the survival of MM patients.The VCAN mRNA and CCND1 mRNA expression in the peripheral blood of MM patients with different ISS was compared.Kaplan-Meier method was used to draw the survival curve of MM,and multi-factor COX proportional regression analysis was established to analyze the factors affecting the prognosis of MM patients.Results The expressions of VCAN mRNA(2.69±0.63)and CCND1 mRNA(3.29±0.63)in peripheral blood of MM group were higher than those of control group(1.32±0.46,1.53±0.37),and the differences were statistically significant(t=18.659,25.473,all P<0.05).The expressions of VCAN mRNA(3.05±0.31)and CCND1 mRNA(3.75±0.21)in peripheral blood of stage Ⅲ group were higher than those of stage Ⅱ(2.76±0.31,3.29±0.36)and stage Ⅰ groups(2.36±0.25,2.95±0.29),and the differences were statistically significant(t=7.626～16.831,all P<0.05).During the follow-up period,1 case was lost to follow-up,36 cases died and 84 cases survived.The overall survival rate of patients with high VCAN mRNA(58.06%)and CCND1 mRNA(57.14%)expression MM was lower than that of patients with low VCAN mRNA(82.76%)and CCND1 mRNA(84.21%),and the differences were statistically significant(χ2=8.727,10.820,all P<0.05).The age of the death group was higher than that of the survival group(t=3.020),ISS stage III,and bone marrow cells proportion≥60%,chromosome karyotype 1q21+proportion,peripheral blood VCAN mRNA and CCND1 mRNA i expression were all higher than those of the survival group(t/χ2=5.988～8.589),and the differences were statistically significant(all P<0.05),respectively.Multivariate COX risk ratio analysis,ISS stage III,high expression of VCAN mRNA and CCND1 mRNA were risk factors for death in MM patients during follow-up(Wald χ2=10.672,5.682,5.969,all P<0.05).Conclusion The expression of VCAN mRNA and CCND1 mRNA in peripheral blood of MM patients is significantly increased,which is related to high clinical stage and poor prognosis.

ObjectiveTo investigate the effects of Buzhong Yiqitang on the abnormal expression of pulmonary surfactant-associated protein C （SFTPC） and lung injury induced by chronic intermittent hypoxia （CIH） and the mechanism of action. MethodsForty healthy adult male SPF-grade C57BL/6 mice were randomly allocated into five experimental groups： a normoxia group， a CIH group， and low-， medium-， and high-dose Buzhong Yiqitang groups， with eight mice in each group. During the modeling， mice in the normoxia group were housed under standard oxygen concentrations， while the CIH and all Buzhong Yiqitang groups were placed in a hypoxic chamber for 8 h daily over 35 d. Prior to each chamber session， mice in the low-， medium-， and high-dose Buzhong Yiqitang groups were administered decoctions by gavage at corresponding doses （8.1， 16.2， 32.4 g·kg^-1·d^-1 of crude drug， respectively）， while those in normoxia and CIH groups received an equivalent volume of saline by gavage. The general conditions of the mice were recorded before and after the experiment. Pulmonary function was assessed using a non-invasive detection system. Serum SFTPC levels were measured using enzyme-linked immunosorbent assay （ELISA）. Histopathological changes in lung tissue were evaluated using hematoxylin-eosin （HE） staining. Apoptosis in lung tissue was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL）. Protein expression of SFTPC， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， protein kinase R-like endoplasmic reticulum kinase （PERK）， phosphorylated PERK （p-PERK）， eukaryotic initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， activating transcript factor 4 （ATF4）， and CCAAT/enhancer-binding protein homologous protein （CHOP） in lung tissue was analyzed by Western blot. Immunofluorescence staining was employed to assess the expression of SFTPC and CHOP proteins in lung tissue. ResultsCompared to those in the normoxia group， mice in the CIH group showed significantly impaired pulmonary function and increased histopathological lung injury scores （P<0.05， P<0.01）. Serum SFTPC levels increased， while SFTPC expression in lung tissue was reduced （P<0.05， P<0.01）. The rate of apoptotic cells in lung tissue increased， and the expression of endoplasmic reticulum stress markers p-PERK， p-eIF2α， ATF4， and CHOP was upregulated （P<0.05， P<0.01）. Compared with the CIH group， Buzhong Yiqitang intervention improved pulmonary function indicators and decreased the histopathological lung injury scores （P<0.05， P<0.01）. Serum SFTPC levels were decreased， and lung tissue SFTPC expression was recovered （P<0.05， P<0.01）. The apoptotic rate of lung tissue cells was significantly reduced， with downregulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2 expression （P<0.05， P<0.01）. Activation and expression of p-PERK， p-eIF2α， ATF4， and CHOP were also decreased （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can alleviate lung injury and improve pulmonary function by reducing lung cell apoptosis and enhancing alveolar surfactant secretion， which may be related to the modulation of the PERK/eIF2α/ATF4/CHOP signaling pathway.

Objective To investigate the potential role of estrogen in the formation of granulation tissue hyperplasia-induced tracheal stenosis in rats.Methods Twenty-four female SD rats were ran-domly divided into three groups(n=8)using a random number table method:sham group(n=8),ovariectomized(OVX)group(bilateral ovariectomy,n=8),and ovariectomized+estrogen(OVX+E2)group(bilateral ovariectomy followed by exogenous estrogen intervention,n=8).Four weeks af-ter establishment of the Sham and OVX rat models,a granulation tissue hyperplasia-induced tracheal stenosis model was constructed in all rats using the oral nylon brush scraping method.On the first day of modeling,rats in the OVX+E2 group were administered 17β-E2 at a dose of 300 μg/kg via intrap-eritonealinjection daily,while rats in the other two groups were given the same volume of normal saline.After 7 consecutive days of administration,tracheal specimens were obtained.Hematoxylin and eosin(HE)staining was used to observe the pathological changes of tracheal granulation tissue hyperplasia in each group and calculate the tracheal stenosis rate.Masson staining was employed to analyze the collagen fibers in the tracheal granulation tissue and calculate the relative collagen deposition area.Immunohistochemical(IHC)staining was used to detect the protein expression levels of transforming growth factor-beta 1(TGF-β 1),vascular endothelial growth factor(VEGF),alpha-smooth muscle actin(α-SMA),and collagen type Ⅰ(COL-Ⅰ)in the tracheal granulation tissue,and the average optical density(AOD)was calculated.Results HE staining revealed granulation tissue hyperplasi-a and tracheal lumen stenosis in the tracheal walls of all three groups.The stenosis rate was the highest in the OVX+E2 group,followed by the sham group,and the lowest in the OVX group,with statistically significant differences(P＜0.05).Masson staining showed that the collagen fibers in the sham group were thicker and denser with more collagen deposition compared to the OVX group.In contrast,the OVX+E2 group had even thicker and denser collagen fibers with more collagen dep-osition than the sham group.IHC staining demonstrated that the protein expression levels of COL-Ⅰ,TGF-β1,VEGF,and α-SMA in the tracheal granulation tissue were the lowest in the OVX group,fol-lowed by the sham group,and the highest in the OVX+E2 group.Conclusion Estrogen can acceler-ate tracheal granulation tissue hyperplasia by upregulating the protein expression levels of COL-Ⅰ,TGF-β1,and VEGF,as well as promoting fibroblast activation,leading to aggravated tracheal stenosis.

Objective To investigate the relationship between the levels of Versican(VCAN)and Cyclin D1(CCND1)in peripheral blood and the progression and prognosis of multiple myeloma(MM).Methods A total of 121 patients with MM(MM group)and 109 healthy volunteers(control group)were selected and admitted to the Department of Hematology of Suzhou Municipal Hospital from January 2018 to May 2022.According to the International Staging System(ISS),the patients with MM were divided into a stage I group(n=46),a stage II group(n=41),and a stage III group(n=34).Real time fluorescence quantitative PCR(RT-PCR)was used to detect the expression levels of VCAN mRNA and CCND1 mRNA in peripheral blood,the patients were followed up for 24 months after discharge to make statistics on the survival of MM patients.The VCAN mRNA and CCND1 mRNA expression in the peripheral blood of MM patients with different ISS was compared.Kaplan-Meier method was used to draw the survival curve of MM,and multi-factor COX proportional regression analysis was established to analyze the factors affecting the prognosis of MM patients.Results The expressions of VCAN mRNA(2.69±0.63)and CCND1 mRNA(3.29±0.63)in peripheral blood of MM group were higher than those of control group(1.32±0.46,1.53±0.37),and the differences were statistically significant(t=18.659,25.473,all P<0.05).The expressions of VCAN mRNA(3.05±0.31)and CCND1 mRNA(3.75±0.21)in peripheral blood of stage Ⅲ group were higher than those of stage Ⅱ(2.76±0.31,3.29±0.36)and stage Ⅰ groups(2.36±0.25,2.95±0.29),and the differences were statistically significant(t=7.626～16.831,all P<0.05).During the follow-up period,1 case was lost to follow-up,36 cases died and 84 cases survived.The overall survival rate of patients with high VCAN mRNA(58.06%)and CCND1 mRNA(57.14%)expression MM was lower than that of patients with low VCAN mRNA(82.76%)and CCND1 mRNA(84.21%),and the differences were statistically significant(χ2=8.727,10.820,all P<0.05).The age of the death group was higher than that of the survival group(t=3.020),ISS stage III,and bone marrow cells proportion≥60%,chromosome karyotype 1q21+proportion,peripheral blood VCAN mRNA and CCND1 mRNA i expression were all higher than those of the survival group(t/χ2=5.988～8.589),and the differences were statistically significant(all P<0.05),respectively.Multivariate COX risk ratio analysis,ISS stage III,high expression of VCAN mRNA and CCND1 mRNA were risk factors for death in MM patients during follow-up(Wald χ2=10.672,5.682,5.969,all P<0.05).Conclusion The expression of VCAN mRNA and CCND1 mRNA in peripheral blood of MM patients is significantly increased,which is related to high clinical stage and poor prognosis.

ObjectiveTo understand the epidemiological characteristics of syphilis in Ruian City, so as to provide a scientific basis for developing syphilis prevention and control strategies. MethodsDescriptive epidemiological methods were used to investigate the infection status of syphilis cases reported among the permanent resident population in Ruian City from 2014 to 2023, and its epidemiological characteristics were analyzed. ResultsA total of 5 482 syphilis cases were reported in Ruian from 2014 to 2023, with a male-female ratio of 1∶1.47. The average annual incidence rate from 2014 to 2023 was 37.51/100 000, with a declining trend in the incidence rate among females (APC=-4.78%, P<0.05). The incidence of primary and secondary syphilis decreased, while the proportion of latent syphilis cases increased. No cases of congenital syphilis were reported from 2017 to 2023. The majority of cases (60.29%) were reported among individuals aged 20‒<50 years. In terms of occupation, the highest proportion was found among housekeepers and the unemployed, constituting 42.70% the total cases. Dermatology departments reported the most cases in medical institutions, accounting for 33.38% of the total cases. The most likely route of infection was heterosexual transmission, accounting for 85.84%. ConclusionThe incidence of syphilis among females in Ruian City shows a declining trend, but the overall situation remains concerning. Prevention and control efforts should be intensified among key groups and high-risk populations, along with an enhancement on health education to curb the spread of syphilis.

Objective To explore the effect of urine mixing degree on 24-hour urinary total protein(24 h UTP)in patients with chronic kidney disease(CKD).Methods From October 1,2023 to December 31,2023,30 hospitalized patients who needed to complete 24 h UTP testing in Zhongshan Hospital,Fudan University were selected.A 5 L unified container was used to collect urine for 24 hours.After collection and one hour's standing,the urine sample was divided into upper,middle,and lower equal parts according to volume,which was defined as direct-sampling group.Then,the urine samples were fully mixed with a magnetic stirrer and sampled again according to the above-mentioned three-equal sampling method,which was defined as mixed-sampling group.The generalized estimating equation was used to compare the urinary protein concentration before and after mixing and at different sampling location.Results The results of generalized estimating equation showed that after controlling the variable"sampling position",there was no significant difference in urinary protein concentration between the direct-sampling group and the mixed-sampling group.After controlling the variable"mixing method",there was still no significant difference in urinary protein concentration at different sampling positions.After adjusting the covariates such as age,gender,and estimated glomerular filtration rate(eGFR),the results were consistent.Conclusions With standard protocol,the entire 24-hour urine sample is a relatively even-distributed solution.After the total urine collection is completed,the temporary sample can be directly extracted from any level of the original urine within 1 hour,and the urine protein concentration of the sample multiplied by the urine volume can reflect the 24 h UTR.

ObjectiveTo investigate the intervention effect of Buzhong Yiqitang （BZYQT） on pulmonary inflammation in mice induced by chronic intermittent hypoxia （CIH） and preliminarily elucidate its mechanism. MethodForty healthy male C57BL/6 mice aged 6-8 weeks were randomly divided into the following groups： normoxia group， model group （exposed to CIH）， and low-， medium-， and high-dose BZYQT groups. The normoxia group was exposed to a normoxic environment， while the model group and the low-， medium-， and high-dose BZYQT groups were exposed to intermittent hypoxia. In the BZYQT groups， the BZYQT （8.1， 16.2， 32.4 g·kg^-1·d^-1） was administered orally 30 min before placing the mice in the hypoxic chamber， while the model group and the normoxia group received an equivalent volume of normal saline. After five weeks of modeling， pulmonary function of the mice was measured using an EMKA animal lung function analyzer， and lung tissue samples were collected after the pulmonary function tests. Hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the lung tissue of each group. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-6 （IL-6）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α） in the serum， as well as angiotensin Ⅱ （Ang Ⅱ） and angiotensin-（1-7） ［Ang（1-7）］ in lung tissue. Western blot and immunohistochemistry were used to detect the protein expression of IL-6， IL-8， TNF-α， angiotensin-converting enzyme 2 （ACE2）， and mitochondrial assembly receptor （Mas）. ResultCompared with the normoxia group， the model group showed significant abnormalities in lung function （P<0.05， P<0.01）， lung tissue changes， such as thickening of alveolar walls and inflammatory cell infiltration， increased levels of IL-6， IL-8， TNF-α in the serum and Ang Ⅱ in lung tissue （P<0.01）， decreased level of Ang（1-7） （P<0.01）， increased protein expression of IL-6， IL-8， and TNF-α， and decreased protein expression of ACE2 and Mas （P<0.05， P<0.01）. Compared with the model group， the BZYQT groups showed improvement in lung function （P<0.05， P<0.01）， and HE staining of lung tissue showed approximately normal alveolar wall thickness and reduced inflammatory cell infiltration. Immunohistochemistry and Western blot analysis showed a significant decrease in the expression of inflammatory-related proteins （P<0.05， P<0.01）， and a significant increase in ACE2 and Mas protein expression （P<0.05， P<0.01）. ConclusionBZYQT can improve lung injury in mice exposed to CIH by regulating the ACE2-Ang（1-7）-Mas axis to inhibit inflammatory responses.

Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH₂) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH₂) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.