Loganin(LOG),a bioactive compound derived from Cornus officinalis Siebold & Zucc,has been understudied in the context of osteoarthritis(OA)treatment.In this study,we induced an inflammatory response in chondrocytes using lipopolysaccharide(LPS)and subsequently treated these cells with LOG.We employed fluorescence analysis to quantify reactive oxygen species(ROS)levels and measured the expression of NLRP3 and nuclear factor erythropoietin-2-related factor 2(NRF2)using real-time quantitative polymerase chain reaction(qRT-PCR),Western blotting,and immunofluorescence(IF)techniques.Additionally,we developed an OA mouse model by performing medial meniscus destabilization(DMM)surgery and monitored disease progression through micro-com-puted tomography(micro-CT),hematoxylin and eosin(H&E)staining,safranin O and fast green(S&F)staining,and immunohisto-chemical(IHC)analysis.Our results indicate that LOG significantly reduced LPS-induced ROS levels in chondrocytes,inhibited the activation of the NLRP3 inflammasome,and enhanced NRF2/heme oxygenase 1(HO-1)signaling.In vivo,LOG treatment mitigated cartilage degradation and osteophyte formation triggered by DMM surgery,decreased NLRP3 expression,and increased NRF2 expres-sion.These findings suggest that LOG has a protective effect against OA,potentially delaying disease progression by inhibiting the ROS-NLRP3-IL-1β axis and activating the NRF2/HO-1 pathway.

Objective:To investigate the correlation between moderate intensity aerobic exercise and cerebral blood flow regulation in patients with mild carotid artery stenosis.Methods:A retrospective study was conducted to select 30 cases of patients with unilateral mild carotid artery stenosis and moderate intensity aerobic exercise for more than 1 year in the Central Hospital of Dalian University of Technology from July 2022 to November 2023 as the exercise group (study group), and 30 cases of patients with unilateral mild carotid artery stenosis without exercise habits matched by age, gender and other factors as the non-exercise group (control group). Transcranial Doppler ultrasound (TCD) examination was performed in both groups, and the recumbent-upright-test, breath holding test and breath exchange test were performed to calculate the occurrence rate of "w" wave in recumbent-upright position, the slope of "w" wave in recubitus position, the change rate of pulse index (PI) before and after breath holding, resistance index (RI), breath holding index (BHI), and cerebral blood flow velocity before and after breath exchange. The blood pressure and heart rate difference in the recumbent-upright position were calculated, and the correlation between moderate intensity aerobic exercise and cerebral blood flow regulation function in patients with mild carotid artery stenosis was evaluated by statistical analysis. The correlation analysis between the exercise years and BHI in the study group was carried out to explore the relationship between the exercise years and cerebrovascular reactivity.Results:The occurrence rate and slope of "w" wave in the study group were higher than those in the control group: 93.3%(28/30) vs. 86.7%(26/30), 2.27 ± 1.14 vs. 1.28 ± 0.23, 2.67 ± 0.63 vs. 1.41 ± 0.69, there were statistically significant ( P<0.05). The change rates of PI and RI before and after breath holding and ventilation in the study group were higher than those in the control group: 21.23 ± 7.67 vs. 13.89 ± 9.67, 14.62 ± 6.63 vs. 11.17 ± 1.78 and 26.26 ± 12.46 vs. 18.36 ± 12.13, 14.91 ± 4.91 vs. 10.83 ± 2.35, and the average cerebral blood flow velocity before and after ventilation was higher than that in the control group: (31.26 ± 4.92) cm/s vs. (24.89 ± 6.34) cm/s, there were statistically significant ( P<0.01). The exercise years of the study group was negatively correlated with the breath holding index. Conclusions:Moderate intensity exercise is associated with cerebral blood flow regulation in patients with mild carotid artery stenosis. Exercise years are negatively correlated with cerebral blood flow regulation. Impaired cerebral blood flow regulation may be one of the potential mechanisms of poor prognosis of stroke in carotid artery stenosis population.

Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD). Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically searched.Meta-analyses of the genetic variants were conducted using at least five data sources.The epidemiologic credibility of the significant associations was graded using the Venice criteria. Results Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing studies.We identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the meta-analysis.The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR). Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.

BACKGROUND:Knee osteoarthritis is a common disease in middle-aged and elderly people.It is a kind of disease that seriously affects the quality of life of patients and even has the risk of disability.Therefore,the pathogenesis and treatment of knee osteoarthritis have become the focus of research.In Chinese medicine,knee osteoarthritis is often treated as"biness,"which is closely related to"biness"caused by blood stasis and blood vessels blocking collaterals in the theory of"blood stasis"in traditional Chinese medicine.Iron overload is a kind of pathological state caused by iron metabolism disorder,which highly coincides with the pathogenic characteristics and clinical manifestations of the"blood stasis"theory of traditional Chinese medicine,and is a risk factor that promotes the development of knee osteoarthritis. OBJECTIVE:Based on the"blood stasis"theory,to summarize the effects of iron overload on cartilage metabolism and subchondral bone reconstruction,to lay a new theoretical foundation for the treatment of knee osteoarthritis with traditional Chinese medicine,and to explore the therapeutic effect of traditional Chinese medicine for promoting blood circulation after interfering with bone tissue. METHODS:CNKI,WanFang database,PubMed and Web of Science databases were searched for relevant literature.The Chinese search terms were"ferroptosis,iron,iron overload,osteoarthritis,blood stasis"and the English search terms were"ferroptosis,iron,iron overload,osteoarthritis,TCM."In the end,76 articles were included for further review. RESULTS AND CONCLUSION:First of all,we explored the potential of the"blood stasis"theory in treating knee osteoarthritis,and found that"blood stasis"is a crucial part in the progress of knee osteoarthritis,indicating that the"blood stasis"theory is the key to the treatment of knee osteoarthritis in traditional Chinese medicine.Secondly,"blood stasis"and iron overload have a high degree of similarity in pathogenic factors,clinical manifestations,and pathogenic characteristics,suggesting the possibility of"blood stasis"theory in treating iron overload.This finding reminds us that iron overload may be an important mechanistic basis for the"blood stasis"theory in the treatment of knee osteoarthritis.The extracts of blood-activating drugs can relieve iron overload and treat knee osteoarthritis,but the specific mechanism is still unclear.Therefore,we believe that the relationship between"blood stasis"theory and iron overload and related mechanisms are important research directions for knee osteoarthritis in the future.The related mechanism of"blood stasis"theory to alleviate iron overload and then treat knee osteoarthritis also provides a theoretical basis for the modernization of traditional Chinese medicine,such as the development of new drugs and innovative usage,and has certain guiding significance for clinical practice.

Objective:To establish a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of voliconazole (VRC), posaconazole (PCZ), and linazolam (LNZ) in human serum.Methods:This study is a methodological validation by LC-MS/MS. The blood concentration results of VRC, PCZ, and LNZ in our hospital′s anti-infection patients were collected. Voriconazole, Posaconazole, and Linezolid were accurately weighed and prepared. Linezolid-[2H3] was used as the internal standard. After gradient elution on the ACE PFP column, the residuals were analyzed by LC-MS/MS in the positive electrospray ionization mode and multiple reaction monitor (MRM) mode. The method′s linearity, precision, lower limit of detection, and recovery rate were validated according to standard guidelines.Results:The linear correlation coefficient ( r) of the standard curve was above 0.99 ( r>0.99). The linear range of VRC and PCZ were 0.10 mg/L~10.00 mg/L, and the lower limit of detection were 0.01 mg/L. The linear range of LNZ was 0.50 mg/L~50.00 mg/L, and the lower limit of detection was 0.05 mg/L. The recoveries of VRC, PCZ and LNZ were 90.96%-103.18%, 91.84%-99.17%, and 97.04%-100.41%, respectively. Intra-and inter-batch precision (% CV) for VRC were less than 8.30%. Intra-and inter-batch precision (% CV) for PCZ was less than 9.78%. Intra-and inter-batch precision (% CV) for LNZ was less than 7.14%. Drug concentrations in 155 cases of VRC, 44 cases of PCZ, and 59 cases of LNZ were detected. Conclusion:We have established an LC-MS/MS method for the rapid, accurate, highly specific determination of VRC, PCZ, and LNZ concentrations in human serum. This method is suitable for analyzing large clinical sample sets.

Objective:To explore the teaching effect of high-fidelity simulation teaching in emergency and critical care nursing course.Methods:From March to June 2019, 56 four-year nursing undergraduates from Xiamen Medical College in 2016 were selected as research subjects by convenient sampling. The high-fidelity simulation teaching was carried out in the emergency and critical care nursing course. The Jeffries Simulation Design Scale (SDS) and open-group interviews were used to evaluate the learning effect.Results:Among 56 students, scores of simulation teaching confidence and satisfaction were (3.80±0.80) and (4.00±0.62) respectively. Group interviews showed that students directly applied the theoretical knowledge they had learned to work situations, and students enhanced their self-learning ability and reflected on operational errors in simulation so as to provoke thinking and enhance learning confidence and personal learning ability.Conclusions:The application of high-fidelity simulation teaching in emergency and critical care nursing course can improve the self-confidence, teamwork ability and comprehensive quality of nursing undergraduates, and increase teaching satisfaction, which is feasible.

Objective:To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations.Methods:The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR.Results:From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission.Conclusion:It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.

Objective:To explore the association between nighttime sleep duration and semen quality.Methods:By using a cross-sectional study, 3357 men were investigated by questionnaire for nighttime sleep duration, the time of falling asleep and falling asleep duration in the Reproductive Center of Shenzhen People's Hospital from August 2017 to August 2018. Semen quality parameters were obtained by computer-aided semen analysis system (CASA). Multiple linear regression was used to analyze the relationship between nighttime sleep duration and semen quality parameters. According to age and body mass index (BMI) stratification, the relationship between nighttime sleep duration and semen quality parameters was further discussed.Results:Compared with males with nighttime sleep duration between 6-8 h, the sperm progressive motility and total motility were 49.15% and 59.49%, respectively, which were significantly lower in the males with nighttime sleep duration≥8 h after adjusting for age, BMI, abstinence time, exercise, drinking and smoking, with regression coefficients, β=-3.16, 95% confidence interval ( CI)=-5.77--0.55 and β=-3.22, 95% CI=-5.93--0.51, respectively. Compared with the shortest duration of falling asleep group (<10 min), the increase of falling asleep duration was related to the decrease of sperm progressive motility ( P=0.045). The total sperm motility of falling asleep duration between 31-60 min group was also significantly lower than that of the shortest falling asleep duration group （ β=-3.80, 95% CI=-6.54--1.06, P=0.007）. Further stratification analysis showed that among the subjects aged 35 to 39 years, the sperm progressive motility of men with nighttime sleep duration less than 6 h was lower than that of 6-8 h group ( β=-4.01, 95% CI=-7.84-0.18, P=0.04). And among the subjects aged more than 40 years, the total sperm number of the men who slept ≥8 h at night was lower than that of the men with nighttime sleep duration between 6-8 h （percentage changes: -47.84%, 95% CI=-72.29%--2.19%, P=0.04）. The progressive and total sperm motility of men with BMI≥24 kg/m 2 and nighttime sleep duration ≥8 h were lower than those with BMI≥24 kg/m 2 in 6-8 h nighttime sleep duration group, and the corresponding regression coefficients were β=-5.75, 95% CI=-10.40--1.10, P=0.02 and β=-6.85, 95% CI=-11.69--2.00, P=0.01. Conclusion:In men ≥40 years old or BMI≥24 kg/m 2, the nighttime sleep duration ≥8 h were associated with the decreased sperm progressive motility and total motility.

Objective:To explore the association between nighttime sleep duration and semen quality.Methods:By using a cross-sectional study, 3357 men were investigated by questionnaire for nighttime sleep duration, the time of falling asleep and falling asleep duration in the Reproductive Center of Shenzhen People's Hospital from August 2017 to August 2018. Semen quality parameters were obtained by computer-aided semen analysis system (CASA). Multiple linear regression was used to analyze the relationship between nighttime sleep duration and semen quality parameters. According to age and body mass index (BMI) stratification, the relationship between nighttime sleep duration and semen quality parameters was further discussed.Results:Compared with males with nighttime sleep duration between 6-8 h, the sperm progressive motility and total motility were 49.15% and 59.49%, respectively, which were significantly lower in the males with nighttime sleep duration≥8 h after adjusting for age, BMI, abstinence time, exercise, drinking and smoking, with regression coefficients, β=-3.16, 95% confidence interval ( CI)=-5.77--0.55 and β=-3.22, 95% CI=-5.93--0.51, respectively. Compared with the shortest duration of falling asleep group (<10 min), the increase of falling asleep duration was related to the decrease of sperm progressive motility ( P=0.045). The total sperm motility of falling asleep duration between 31-60 min group was also significantly lower than that of the shortest falling asleep duration group （ β=-3.80, 95% CI=-6.54--1.06, P=0.007）. Further stratification analysis showed that among the subjects aged 35 to 39 years, the sperm progressive motility of men with nighttime sleep duration less than 6 h was lower than that of 6-8 h group ( β=-4.01, 95% CI=-7.84-0.18, P=0.04). And among the subjects aged more than 40 years, the total sperm number of the men who slept ≥8 h at night was lower than that of the men with nighttime sleep duration between 6-8 h （percentage changes: -47.84%, 95% CI=-72.29%--2.19%, P=0.04）. The progressive and total sperm motility of men with BMI≥24 kg/m 2 and nighttime sleep duration ≥8 h were lower than those with BMI≥24 kg/m 2 in 6-8 h nighttime sleep duration group, and the corresponding regression coefficients were β=-5.75, 95% CI=-10.40--1.10, P=0.02 and β=-6.85, 95% CI=-11.69--2.00, P=0.01. Conclusion:In men ≥40 years old or BMI≥24 kg/m 2, the nighttime sleep duration ≥8 h were associated with the decreased sperm progressive motility and total motility.

Objective: To explore the association between dust exposure and the incidence of hypertension in male coal miners. Methods: Using the method of retrospective cohort study,a hypertension cohort of colliery in Henan Province was established in January 2006. From 2006 to 2017,all the male coal miners in a colliery who were exposed to dust were selected into the exposure group including tunneling, mining,auxiliary and combining workers, and workers from administrative logistics departments who were not exposed to dust were selected into the control group. The eligible participants should satisfy following conditions: working more than one year, with clear and complete record of occupation change, and with complete archives and reliable diagnosis of occupational health surveillance. The exclusion criteria of participants were with hypertension at the baseline of study or with heart,liver,kidney diseases and malignant tumors. A total of 12 647 participants were enrolled in this study (11 663 in the exposure group and 984 in the control group). The follow-up period was from January 2006 to December 2017,with a total follow-up of 89 259.75 person-years. Questionnaires and physical measurements were used to collect general demographic characteristics, occupational exposure history and occupational health surveillance data of all participants. The Cox proportional hazards regression model was used to estimate the association between the dust exposure and the incidence of hypertension. Results: During the follow-up period, 2 549 new-onset hypertension patients were identified with an incidence density of hypertension about 2 855.71 per 100 000 person-years. The incidence density of hypertension was 2 967.58 per 100 000 person-years in the exposure group, and 1 643.85 per 100 000 person-years in the control group. The results of multivariate Cox proportional hazards regression model showed that after the adjustment of marriage, age, smoking, alcohol drinking and body mass index,the risk of hypertension was higher in the exposure group compared with the control group (HR=1.692, 95%CI: 1.410-2.032). Further analysis showed that compared with workers from administrative logistics departments,the risk of hypertension in tunneling,mining and auxiliary working was 1.629(1.345-1.973),1.677(1.374-2.046) and 1.782(1.475-2.151),respectively. Conclusion Dust exposure may increase the risk of hypertension in male coal miners.