OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

Objective: To investigate the epidemiological characteristics of pulmonary tuberculosis (PTB) among residents aged 60 years and older in Yangzhou City, Jiangsu Province from 2013 to 2022, so as to provide the evidence for the improvement of PTB prevention and control measures in this population. Methods: Data of PTB cases aged 60 years and older in Yangzhou City from 2013 to 2022 were collected from the Chinese Disease Prevention and Control Information System. The temporal, population, and regional distribution characteristics of PTB cases were analyzed using the descriptive epidemiological method. Results: A total of 8 726 PTB cases aged 60 years and older were registered in Yangzhou City from 2013 to 2022, including 4 167 cases positive for pathogenic tests, with a positive rate of 47.75%. The registered incidence rates and the positive rates of pathogenic tests of PTB among residents aged 60 years and older in Yangzhou City showed downward trends from 2013 to 2022 (both P<0.05). The average annual registered incidence rate of PTB was 83.95/105, and the average annual registered incidence rate of PTB positive for pathogenic tests was 40.09/105. The average annual registered incidence rate of PTB in males was higher than that in females (138.57/105 vs. 31.76/105, P<0.05). The registered incidence rate of PTB showed an increasing trend with age (P<0.05), with the highest rate observed in the age group of 75-<80 years (110.37/105). The top three regions with the highest average annual registered incidence rates of PTB were Jiangdu District (94.34/105), Baoying County (91.61/105) and Hanjiang District (84.93/105). Conclusions The registered incidence of PTB among residents aged 60 years and older in Yangzhou City showed a downward trend from 2013 to 2022. Particular attention should be payed to males, residents aged 75- <80 years, and the elderly in Jiangdu District and Baoying County.

Objective: To analyze the association between alcohol consumption and lumbar disc herniation (LDH), so as to provide a reference for the development of prevention and treatment strategies for LDH. Methods: From May to July 2022, permanent residents aged ≥18 years from eight counties (cities/districts) in Gansu Province were selected using a multistage stratified random sampling method. Data on basic characteristics, alcohol consumption in the past 30 days, hypertension, and diabetes mellitus were collected through questionnaire surveys. LDH was determined based on imaging findings, combined with disease history or clinical symptoms. Multivariable logistic regression model was used to analyze the association between alcohol consumption and LDH, with subgroup analyses conducted by gender, age, ethnicity, and altitude of residence. Propensity score matching (PSM) was utilized for sensitivity analysis. Results: A total of 4 545 individuals were surveyed. There were 2 026 (44.58%) males and 2 519 (55.42%) females. The mean age was (44.82±15.33) years. The study participants were predominantly of Han ethnicity, with 2 598 persons accounting for 57.17%. The altitude of residence was mainly above 3 500 m, with 1 941 persons accounting for 42.71%. There were 574 alcohol drinkers, accounting for 12.63%. LDH was detected in 1 035 cases, with a detection rate of 22.77%. Multivariable logistic regression analysis showed that after adjusting for gender, age, physical activity, and hypertension, compared to non-drinking residents, alcohol-consuming residents exhibited a 27.6% reduction in the risk of LDH (OR=0.724, 95%CI: 0.544-0.963). No significant interaction effects on LDH risk were observed between alcohol consumption and gender, age, ethnicity, or altitude of residence (all Pfor interaction >0.05). The results of the sensitivity analysis indicated that compared to non-drinking residents, alcohol-consuming residents exhibited a 38.8% reduction in the risk of LDH (OR=0.612, 95%CI: 0.382-0.976). Conclusion Alcohol consumption was statistically associated with a lower risk of LDH.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective To construct a predictive model for clinical pregnancy outcomes in frozen-thawed embryo transfer(FET)cycles in women with advanced maternal age(age≥35 years)and to analyze its influencing factors.Methods A retrospective analysis was conducted on the clinical data of 2717 older patients who underwent FET treatment at the First Affiliated Hospital of Kunming Medical University from January 2018 to December 2023.These Patients were divided into a clinical pregnancy group(n=851)and a non-clinical pregnancy group(n=1866)based on whether the clinical pregnancy had occurred.The general characteristics and transplantation details of the two groups were compared,and a logistic regression analysis model was constructed.Results The clinical pregnancy rate(CPR)was 31.32%.The CPR for women aged 35-40 years(40.06%)was higher than that for women aged≥40 years(19.35%),with a statistically significant difference(χ2=133.371,P<0.05).The model results showed that the higher anti-Mullerian hormone(AMH)levels(OR=1.053,95%CI:1.012-1.095),the more high-quality blastocysts were transferred(OR=1.704,95%CI:1.143-2.542;OR=2.861,95%CI:1.921-4.262);the more high-quality blastocysts were transferred(OR=2.033,95%CI:1.077-3.836;OR=3.886,95%CI:2.035-7.420),the thicker the endometrial lining on the day of transfer(OR=1.150,95%CI:1.092-1.212)and it could increase the probability of clinical pregnancy.However,for women over 40 years of age(OR=0.551,95%CI:0.437-0.694)and secondary infertility(OR=0.704,95%CI:0.552-0.896),the probability of clinical pregnancy would be reduced;ROC curve analysis results showed that the AUC for predicting clinical pregnancy occurrence in the training set and validation set of the predictive model were 0.723(95%CI:0.699-0.748)and 0.726(95%CI:0.689-0.764),respectively,with cutoff values of 0.262 and 0.260 and the model fit was good(P>0.05).Conclusion Female age,AMH level,type of infertility,number of high-quality embryos(cleavage embryos,blastocysts)transferred,and endometrial thickness on the day of transfer are important factors affecting FET cycles in advanced maternal age women.The constructed prediction model based on these factors has a certain predictive ability for clinical pregnancy.

Objective To analyze the predictive value of serum levels of procalcitonin(PCT)and cytokines on the prognosis of patients with COVID-19 at admission.Methods From November 2022 to February 2023,patients diagnosed with COVID-19 who were admitted to Beijing Chest Hospital were enrolled.Chemiluminescence was used to detect serum PCT levels,and flow microsphere array was used to detect serum cytokines IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17A,IL-17F,IL-22,TNF-α,TNF-β,IFN-γ level.ICU admission,mechanical ventilation and in-hospital death were defined as poor prognosis.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.Results A total of 176 patients with complete data were included,including 134 in the PCT-normal group and 42 in the PCT-elevated group,with a median age of 71.50 years and 71.59%males.Patients in the PCT elevated-group had significantly higher rates of ICU admission(38.41%vs.13.11%,P<0.05),mechanical ventilation(76.92%vs.24.59%,P<0.001)and in-hospital mortality(38.46%vs.6.56%,P<0.001)were significantly higher than those in the PCT-normal group.Serum levels of cytokines IL-6(7.40 pg/mL vs.4.78 pg/mL,P = 0.033 4)and IL-8(10.97 pg/mL vs.5.92 pg/mL,P<0.001)were significantly higher in patients with poor prognosis than in those with good prognosis.The area under the curve for PCT,IL-6,and IL-8 to predict poor prognosis in COVID-19 patients was 0.687,0.660,and 0.746,respectively;sensitivity was 52.78%,55.17%,and 72.41%,respectively;and specificity was 81.58%,74.19%,and 74.19%,respectively,as calculated from the ROC curve.When PCT,IL-6 and IL-8 jointly predict the prognosis of COVID-19 patients,the area under the curve is 0.764,the sensitivity is 70.00%,and the specificity is 80.00%.Conclusion Serum PCT and cytokines IL-6 and IL-8 could be used as predictive markers for poor prognosis in patients with COVID-19.

An elderly female melanoma patient who experienced severe liver injury after treatment with pembrolizumab and axitinib,which improved with glucocorticoid therapy.Through medication analysis and adverse reaction scale evaluated,it was considered that severe liver injury was more closely related to the immune checkpoint inhibitor,pembrolizumab.After a comprehensive analysis of the relationship between liver injury and immunotherapy,as well as the benefits and risks of immunotherapy for patients,immunotherapy was rechallenged 40 days after discontinuation of pembrolizumab.Restarting treatment with pembrolizumab after immune-mediated hepatitis poses a risk of recurrence of hepatotoxicity.After reviewing related literature,it had been found that the incidence of severe hepatotoxicity caused by rechallenging treatment was low,and the overall safety was controllable.Pembrolizumab had brought therapeutic benefits to patients,with no further immune-mediated liver injury of 5 cycles medication.This case can provide a reference for rechallenging immunotherapy after immune-mediated hepatitis.

Information on patients with rifampicin-resistant pulmonary tuberculosis (RR-PTB) in Yangzhou City from 2012 to 2020 was obtained from the Information System of the Chinese Center for Disease Control and Prevention. The epidemic characteristics of RR-PTB patients were analyzed by using χ2 test. The average annual registered incidence rate of RR-PTB patients in Yangzhou City from 2012 to 2020 was 0.57/100 000, and the difference between the registered incidence rates in each year was statistically significant ( χ2=29.326, P<0.001). The proportion of re-treated patients (64.8%) was higher than that of newly treated patients (35.2%, χ2=50.593, P<0.001). The registered incidence rate in males (0.91/100 000) was higher than that in females (0.24/100 000, χ2=80.566, P<0.001). The age distribution showed that the highest incidence rate was in the age group≥60 years (0.96/100 000) and the lowest was in the age group 0-<45 years (0.31/100 000, χ2=55.853, P<0.001). From 2012 to 2020, Baoying County had the largest number of registered RR-PTB patients (44 cases), and its registered incidence rate (0.64/100 000) was only lower than that of Guangling District (0.98/100 000). The registered incidence rate of RR-PTB patients in Baoying County during 2016—2020 also increased significantly compared to 2012—2015 ( P=0.001). Logistic regression was used to analyze the factors related to the treatment outcome of RR-PTB patients. The results showed that patients aged≥60 years and those classified as the re-treatment were risk factors for successful treatment of RR-PTB patients ( P<0.05). In summary, males, people aged≥60 years, patients classified as the re-treatment, and residents of Baoying County should be the key populations for RR-PTB epidemic prevention and control in Yangzhou City.

Objective:To explore the potential application of two-dimensional speckle tracking echocardiography (2D-STE) in terms of quantification and evaluating left and right atrial function in normal fetuses, and to investigate the relevant factors affecting left and right atrial function in normal fetuses as well as differences between both atrial function.Methods:A total of 100 single fetuses underwent fetal echocardiography in the Department of Diagnostic Ultrasound & Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine from January 2019 to October 2022 were retrospectively enrolled. The standard basal or apical four-chamber view clips were obtained, and the left and right atrial function were quantitatively analyzed using TomTec-ARENA off-line cardiac analysis software for quantitative assessment of both atrial strain measurements including left atrial reservoir phase longitudinal strain (LASr), left atrial ductal phase longitudinal strain (LAScd), left atrial systolic phase longitudinal strain (LASct), right atrial reservoir phase longitudinal strain (RASr), right atrial ductal phase longitudinal strain (RAScd), right atrial systolic phase longitudinal strain (RASct), and the ratio of systolic longitudinal strain to conduit longitudinal strain in left and right atrial systolic display groups were calculated which was denoted as Sct/Scd.Routine fetal obstetric ultrasound measurements and fetal echocardiographic parameters in the two groups were obtained including fetal heart rate (FHR), left atrial end-systolic length (LAESL), left atrial end-systolic diameter (LAESD), left atrial end-systolic area (LAESA), left ventricular end-diastolic transverse diameter (LVEDD), right atrial end-systolic length (RAESL), right atrial end-systolic diameter (RAESD), right atrial end-systolic area (RAESA), right ventricular end-diastolic transverse diameter (RVEDD), peak blood flow velocity of mitral valve and tricuspid valve in early and late diastolic period (E, A), peak ratio of E and A: E/A (MV), E/A (TV), and the difference between the left and right atrial strain indices and the routine fetal obstetric ultrasound and fetal echocardiographic parameters, as well as the correlation between the above parameters and gestational age were analyzed. The repeatability tests were performed using the intra-class correlation coefficientt (ICC).Results:Significant differences were found in LASr and RASr, LAScd and RAScd, LASct and LAScd, Sct/Scd between the left atrium and right atrium, E/A (MV) and E/A (TV), LAESD and RAESD, LAESL and RAESL (all P<0.05), there was significant difference in FHR between the left atrial contraction display group and the no atrial contraction display group ( P=0.011), no significant difference in other parameters (all P>0.05). Correlation analysis showed that, LASr, LASct, RASr, and RASct showed moderate negative correlation with gestational age ( rs=-0.570, -0.601, -0.469, -0.568; all P<0.001). While LAScd, RAScd, E/A (MV), E/A (TV) were moderately positively related with gestational age ( rs=0.310, 0.350, 0.330, 0.343; all P<0.05). LAESL, LAESD, LAESA, RAESL, RAESD, RAESA, LVEDD and RVEDD were significantly positively related with gestational age ( rs=0.662, 0.768, 0.792, 0.728, 0.828, 0.822, 0.838, 0.802, all P<0.001). The inter-examiner ICC of fetal LASr and RASr were 0.89 and 0.84 (both P<0.05) and the intra-examiner ICC of fetal RASr and LASr both were 0.80 (both P<0.05), with good consistency. Conclusions:2D-STE is highly feasible and reproducible in assessing fetal atrial function. The corresponding variation values of fetal atria at different gestational weeks were obtained in this study, which provides a new reference index for us to further study normal fetal atria as well as comparative analysis of fetal cardiac function under prenatal pathological conditions.

Objective:To explore the potential application of two-dimensional speckle tracking echocardiography (2D-STE) in terms of quantification and evaluating left atrial function in normal fetuses and fetuses with left ventricular outflow tract obstruction (LVOTO).Methods:A total of 32 fetuses diagnosed with LVOTO, who underwent fetal echocardiography at Sir Run Run Shaw Hospital, Zhejiang University College of Medicine between May 2020 to June 2022, were selected as the case group, and 100 pregnant women with normal singleton fetuses between January 2019 to October 2022 were chosen as the control group. The standard basal or apical four-chamber view clips were obtained and were quantitatively analyzed using TomTec-Arena off-line cardiac analysis software to obtain the left atrial strain parameters of the two groups of fetuses including left atrial reservoir phase longitudinal strain(LASr), left atrial ductal phase longitudinal strain(LAScd), left atrial systolic phase longitudinal strain (LASct), as well as the routine obstetric ultrasound measurements and fetal echocardiographic parameters of the two groups: biparietal diameter (BPD), femur length (FL), aortic annulus end-systolic inner diameter (AO), pulmonary annulus end-systolic inner diameter (PA), left atrial end-systolic long length (LAESL), left atrial end-systolic transverse diameter (LAESD), right atrial end-systolic long length (RAESL), right atrial end-systolic transverse diameter (RAESD), left ventricular end-diastolic transverse diameter (LVEDD) and right ventricular diastole end-diastolic transverse diameter (RVEDD). The ratio of right ventricular end-diastolic transverse diameter to left ventricular end-diastolic transverse diameter (RVd/LVd) and the ratio of pulmonary annulus diameter to aortic annulus diameter (PA/AO) were calculated. The differences of strain parameters between the two groups were compared, and the correlation between strain parameters and gestational age, RVd/LVd and other conventional measurement parameters were analyzed. ROC curve was used to compare the specificity and sensitivity of LASr and RVd/LVd in evaluating fetal cardiac dysfunction with LVOTO.Results:There were significant differences in LASr, LAScd, LASct, MAPSE, AO, LAESL, LVEDD, RVd/LVd and PA/AO between the two groups (all P<0.05), there were no significant differences in other parameters (all P>0.05). Correlation analysis showed that LASr was negatively correlated with RVd/LVd in LVOTO group ( rs=-0.394, P=0.025), and LASct was negatively correlated with RVd/LVd ( rs=-0.626, P=0.004). In the control group, LASr was negatively correlated with gestational age, AO and PA ( r/ rs=-0.570, -0.440, -0.493; all P<0.001), and LASct was negatively correlated with gestational age, AO and PA ( r/ rs=-0.601, -0.532, -0.568; all P<0.001). LAScd was positively correlated with gestational age, AO and PA ( r/ rs=0.310, 0.370, 0.314; all P<0.05). There were no significant correlations between the other parameters (all P>0.05). ROC curve analysis showed that the area under the curve(AUC) in LASr evaluation of fetal cardiac dysfunction with LVOTO was 0.890 (0.826, 0.953) and the AUC in RVd/LVd evaluation of fetal cardiac dysfunction with LVOTO was 0.742 (0.637, 0.846), there were significant differences between them( P<0.05). Conclusions:2D-STE is highly feasible and reproducible in assessing fetal left atrial function. Evaluation of fetal left atrial function by 2D-STE provides a new reference index for quantitative analysis of fetal cardiac dysfunction.