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 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.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

Objective To investigate sex-related differences in left ventricular systolic dysfunction in heart failure with preserved ejection fraction(HFpEF)and type 2 diabetes mellitus(T2DM).Methods A total of 228 HFpEF patients who were treated in the Department of Endocrinology and Cardiology of the Second Hospital of Shijiazhuang from January 2019 to June 2023 were enrolled.They were divided into HFpEF group[women(n=61),men(n=73)]and HFpEF+T2DM group[women(n=49),men(n=73)]according to whether they had T2DM.Conventional echocardiography and left ventricular global longitudinal strain(GLS)data were measured.Sex-related differences of left ventricular structure and function were compared between the two groups.Multivariable linear regression analysis was performed for the determinants of impaired left ventricular GLS for HFpEF with T2DM patients and HFpEF patients of both sexes.Results LVMI was lower in women than in men in HFpEF group(P<0.05).The left ventricular remodeling rate of women was higher in HFpEF+T2DM group than that of men and women in HFpEF group,and the GLS of women was lower than that of men and women in HFpEF group(P<0.05).The E/E'was higher in women than in men in HFpEF and HFpEF+T2DM groups(P<0.05).Multivariable linear regression analysis showed that age,women,HbA1c and LVMI were the determinants of GLS impairement in HFpEF patients with T2DM.Age,T2DM,NT-proBNP and LVMI were the determinants of GLS impairement in HFpEF women patients,where as age,BMI,CHD,NT-proBNP and LVMI were the determinants of GLS impairement in HFpEF men patients.Conclusions There are sex-related differences in left ventricular systolic dyfunction in HFpEF with T2DM patients.With T2DM exerting a greater adverse effect onleft ventricular systolic dyfunction in women with HFpEF than men.

AIM:To investigate the therapeutic effect of enteric-coated sustained-release new dosage form of tadalafil on mice with renal fibrosis caused by unilateral ureteral obstruction(UUO).METHODS:Eight-week-old male C57BL/6J mice were divided into four groups randomly:sham group,UUO group,UUO+new dosage form of tadalafil(1 mg/kg)group and UUO+original patented drug of tadalafil(5 mg/kg)group.Surgery was performed to create a mouse UUO model,and therapeutic drugs were administered intragastrically for 7 d after modeling.A fully automated biochemi-cal analyzer was used to detect serum creatinine(SCr)levels of each group.Through renal histopathological staining(HE staining,Masson trichrome staining,and immunohistochemistry staining)and Western blot,we assessed the therapeutic effect of enteric-coated sustained-release new dosage forms of tadalafil on kidney fibrosis in mice,as well as its effect on the expression and distribution of fibronectin(FN)and α-smooth muscle actin(α-SMA).RESULTS:Compared with sham group,the SCr levels were significantly increased in mice with renal fibrosis,and renal tubules were dilated and in-filtrated with inflammation.Moreover,the expressions of FN and α-SMA were increased significantly(P<0.05).New dosage form and the original patented drug tadalafil both significantly reduced SCr levels in mice with renal fibrosis,im-proved the renal tissue structure on the affected side,reduced collagen fiber deposition,and inhibited FN and α-SMA ex-pression(P<0.05).CONCLUSION:Enteric-coated sustained-release new dosage form of tadalafil reduces the deposit of extracellular matrix in kidney interstitial tissue and attenuates fibrosis and renal function damage caused by ureteral ob-struction.New dosage form of tadalafil has significant advantages over the original patented drug because the low dose and high effectiveness.

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.