Objective: To reveal the molecular mechanism underlying the compatibility of Salvia miltiorrhiza Bge (S. miltiorrhiza, Dan Shen) and C. tinctorius L. (C. tinctorius, Hong Hua) as an herb pair through network pharmacology and subsequent experimental validation. Methods: Network pharmacology was applied to construct an active ingredient-efficacy target-disease protein network to reveal the unique regulation pattern of S. miltiorrhiza and C. tinctorius as herb pair. Molecular docking was used to verify the binding of the components of these herbs and their potential targets. An H9c2 glucose hypoxia model was used to evaluate the efficacy of the components and their synergistic effects, which were evaluated using the combination index. Western blot was performed to detect the protein expression of these targets. Results: Network pharmacology analysis revealed 5 pathways and 8 core targets of S. miltiorrhiza and C. tinctorius in myocardial protection. Five of the core targets were enriched in the hypoxia-inducible factor-1 (HIF-1) signaling pathway. S. miltiorrhiza-C. tinctorius achieved vascular tone mainly by regulating the target genes of the HIF-1 pathway. As an upstream gene of the HIF-1 pathway, STAT3 can be activated by the active ingredients cryptotanshinone (Ctan), salvianolic acid B (Sal. B), and myricetin (Myric). Cell experiments revealed that Myric, Sal. B, and Ctan also exhibited synergistic myocardial protective activity. Molecular docking verified the strong binding of Myric, Sal. B, and Ctan to STAT3. Western blot further showed that the active ingredients synergistically upregulated the protein expression of STAT3. Conclusion The pharmacodynamic transmission analysis revealed that the active ingredients of S. miltiorrhiza and C. tinctorius can synergistically resist ischemia through various targets and pathways. This study provides a methodological reference for interpreting traditional Chinese medicine compatibility.

Objective:To explore if miR-133a is involved in the occurrence and development of hepatocellular carcinoma(HCC)via regulating G6PD.Methods:Bioinformatics analysis predicted the binding sites of miR-133a and G6PD;RT-PCR or western blot was used to assess the expres-sion of miR-133a and G6PD in HCC tissues and the adjacent normal tissues;CCK-8 and flow cy-tometry assays were performed to evaluate the effects of miR-133a/G6PD on cell proliferation,apop-tosis;Fluorescent reporter gene and western blot assays were used to assess the effect of miR-133a on G6PD expression.Results:miR-133a expression was decreased in HCC tissues while G6PD was increased(P0.01);Up-regulation of miR-133a significantly reduced G6PD expression(P＜0.01);up-reg-ulation of miR-133a inhibited cell growth and promoted cell apoptosis(P＜0.05),whereas these effects induced by miR-133a over-expression were all abolished when G6PD was up-regulated(P＜0.01).Conclusion:miR-133a represses the occurrence and development of HCC via targeting G6PD.

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides (MOIG) on bone loss of rheumatoid arthritis (RA) rats, and the mechanism of osteoclast function and activity induced by lipopolysaccharide (LPS). RA rats were established by injecting bovin type II collagen. The Bio-ethic Committee of Zhejiang Chinese Medical University approved all experimental protocols associated with this study (IACUC-20180410-03). The collagen-induced arthritis (CIA) rats were administered drug by gavage for 8 weeks; the femoral trabecular micro-structure changes were observed in CIA rats by micro-CT; the LPS-induced osteoclasts model further observed the effect and mechanism of anti-inflammatory osteoporosis in vitro. The results indicated that MOIG could markedly increase bone mineral density (BMD) in CIA rats, improve trabecular micro-structure. In vitro studies demonstrated that MOIG could significantly inhibit osteoclastogensis and differentiation, suppress tartrate resistant acid phosphatase (TRAP) activity, F-actin ring formation, TNF receptor associated factor 6 (TRAF6) recruitment, and inhibitor of nuclear factor kappa-Bα (IκBα) degradation as well as p65 phosphorylation, thereby repressing nuclear factor kappa-B (NF-κB) signaling pathway activation. Subsequently, MOIG effectively inhibited osteoclast nuclear factor of activated T-cells c1 (NFATc1) and cellular oncogene Fos (c-Fos) expression, as well as bone resorption related protein activity including matrix metalloprotein 9 (MMP-9) and cathepsin K (CtsK). Meanwhile, MOIG also repressed the phosphorylation expression of Janus activating kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), thereby inhibiting JAK2/STAT3 signaling pathway activation. Moreover, further studies found that MOIG could suppress glycogen synthase kinase-3β (GSK-3β) activity, and GSK-3β gene silencing could markedly inhibit oetsoclast F-actin ring formation as well as the phosphorylation expression of p65 and STAT3. Of note, compared with GSK-3β gene silencing group, there was no significant difference in the group treated with both MOIG with GSK-3β gene silencing simultaneously. Thus, the results suggested that MOIG may inhibit NF-κB signaling pathway and JAK2/STAT3 signaling pathway activation via regulating GSK-3β, thereby alleviating bone destruction in RA.

Objective:To evaluate the value of CEA, CYFRA21-1 and CA125 tests in opportunistic screening of non-small cell lung cancer (NSCLC) based on meta-analysis.Methods:The original research literatures on the diagnostic value of CEA, CYFRA21-1 and CA125 in Chinese NSCLC patients were searched from databases of PubMed, Embase, The Cochrane Library, CNKI, VIP, Database and Wanfang database from establishment to June 2023. The literature screening, data extraction and quality evaluation were carried out independently by two researchers. The quality evaluation tool of diagnostic accuracy studies was used to evaluate the quality of the literature. A summary receiver operating characteristic (SROC) curve was used to assess the overall effectiveness of the tests. The outcome stability and publication bias were detected by using sensitivity analysis and Deeks′ test.Results:A total of 23 studies met the inclusion and exclusion criteria were included. The results of meta-analysis showed that the overall sensitivity of CEA, CYFRA21-1 and CA125 alone in the diagnosis of NSCLC was relatively low, it was 0.49(95% CI: 0.43-0.55), 0.56(95% CI: 0.49-0.63) and 0.41(95% CI: 0.33-0.49), respectively. The overall sensitivity of the combined detection of the three markers for the diagnosis of NSCLC increased to 0.83(95% CI: 0.69-0.91), but the overall specificity decreased to 0.76(95% CI: 0.69-0.83). Conclusions:The single detection of CEA, CYFRA21-1 and CA125 is not recommended for screening NSCLC in population receiving physical examination. Although the sensitivity of the combined detection of CEA, CYFRA21-1 and CA125 for screening NSCLC is improved, but the specificity is decreased, the misdiagnosis rate is increased, so the screening effect is limited.

[Objective]To explore the efficacy of Solifenacin in the treatment of children with idiopathic overactive bladder(OAB).[Methods]The study included 67 children with idiopathic OAB treated in the urology clinic of our hospital from March 2022 to March 2023.After at least 2-week-long behavioral therapy showed no significant therapeutic effect,52 of the cases in the trial group were given oral Solifenacin 5 mg once daily and the other 15 cases in the control group con-tinued the behavioral therapy.The cases in trial group were subdivided into OAB-dry group(27 cases without urinary in-continence)and OAB-wet group(25 cases with urinary incontinence).The 3-day micturition diary,OAB Symptom Scores(OABSS)and the adverse reactions were recorded and analyzed before,at Weeks 2,4,8 and 12 after the treat-ment.[Results]Of all the 67 cases who completed a 3-month follow-up,44 were cured including 41 in the trial group and 3 in the control group,4 presented with adverse reactions.After the 3-month follow-up,the OABSS declined markedly in trial group than in control group(Z=4.524,P<0.001);the cure rates in trial group and control group are 78.8%and 20%respectively,with significant difference(χ2=15.367,P<0.001).At each follow-up,we found increased mean voided vol-ume(F=9.707,P<0.001),reduced mean voiding frequency during daytime(F=3.837,P=0.009)and decreased voiding urgency(χ2=482.835,P<0.001).After the 3-month follow-up,the cure rates in OAB-dry group and OAB-wet group are 81.5%and 76%respectively,with no significant difference(χ2=0.234,P=0.629).[Conclusions]In children with idiopath-ic OAB,oral Solifenacin 5 mg once daily could significantly increase mean voided volume,reduce mean voiding frequency during daytime,relieve symptoms of urinary urgency and lead to fewer adverse reactions,but is not significantly effective for the treatment of urinary incontinence in OAB-wet children.

Objective To analyze the clinical characteristics of high energy metabolism in lung cancer patients and its correlation with body composition,nutritional status,and quality of life,and to develop a corresponding risk prediction model.Methods Retrospectively analyzed 132 primary lung cancer patients admitted to the First Hospital of Shanxi Medical University from January 2022 to May 2023,and categorized into high(n=94)and low energy metabolism group(n=38)based on their metabolic status.Differences in clinical data,body composition,Patient Generated Subjective Global Assessment(PG-SGA)scores,and European Organization for Research and treatment of Cancer(EORTC)Quality of Life Questionnaire-Core 30(QLQ-C30)scores were compared between the two groups.Logistic regression was used to identify the risk factors for high energy metabolism in lung cancer patients,and a risk prediction model was established accordingly;the Hosmer-Lemeshow test was used to assess the model fit,and the ROC curve was used to test the predictive efficacy of the model.Results Of the 132 patients with primary lung cancer,94(71.2%)exhibited high energy metabolism.Compared with low energy metabolism group,patients in high-energy metabolism group had a smoking index of 400 or higher,advanced disease staging of stage Ⅲ or Ⅳ,and higher levels of IL-6 level,low adiposity index,low skeletal muscle index,and malnutrition(P<0.05),and lower levels of total protein,albumin,hemoglobin level,and prognostic nutritional index(PNI)(P<0.05).There was no significant difference in age,gender,height,weight,BMI and disease type between the two groups(P>0.05).Logistic regression analysis showed that smoking index≥400,advanced disease stage,IL-6≥3.775 ng/L,and PNI<46.43 were independent risk factors for high energy metabolism in lung cancer patients.The AUC of the ROC curve for the established prediction model of high energy metabolism in lung cancer patients was 0.834(95%CI 0.763-0.904).Conclusion The high energy metabolic risk prediction model of lung cancer patients established in this study has good fit and prediction efficiency.

Objective:To investigate the timing and features of fine-needle aspiration biopsy (FNAB) guided by ultrasound for Bethesda Ⅲ thyroid nodules and to further optimize the puncture scheme.Methods:A retrospective analysis was conducted on data from patients who underwent rFNAB for Bethesda Ⅲ thyroid nodules at the China-japan Union Hospital of Jilin University Thyroid Surgery Department from Dec. 2020 to Dec. 2022. The study included 71 cases (73 nodules), consisting of 57 females and 14 males, with an average age of (45.7±10.4) years. Patients were grouped based on rFNAB results: Bethesda Ⅱ as the benign group ( n=21), Bethesda Ⅴ/Ⅵ as the malignant group ( n=39), and the remaining cases categorized as the indeterminate group ( n=13). Data on rFNAB results, puncture interval time, postoperative pathology, ultrasound features, and FNAB characteristics were recorded. Descriptive statistics were used for categorical data, presented as percentages and numbers, while continuous data were presented as mean ± standard deviation ( ± s). The χ2 test or Fisher's exact test was applied for analysis. Results:In this study, rFNAB was performed on 73 Bethesda Ⅲ thyroid nodules. The results showed that 60 nodules (82.2%) received a definite diagnosis, while 13 nodules (17.8%) were indeterminate. There was a statistically significant difference in the calcification classification between the malignant group and the benign group as well as the indeterminate group ( P<0.05). Among the malignant group, 29 patients underwent surgical treatment, with only 2 cases (8.0%) showing intermediate recurrence risk when surgery was performed more than three months after the initial FNAB. Upon reevaluation of the 31 initial FNAB samples from the malignant group, 9 samples (29.0%) exhibited mild cytological atypia, and 22 samples (71.0%) had poor quality specimens, mainly comprising fibrous and calcified components. Conclusions:For nodules initially classified as Bethesda Ⅲ, if suspicious ultrasound features persist or emerge, especially if microcalcifications are present, rFNAB should be performed after a follow-up period exceeding three months. However, during the puncture, multiple points should be targeted at the non-calcified areas of the nodule to enhance the accuracy and reliability of rFNAB.

Objective:This study aimed to evaluate the efficacy and safety of venetoclax (VEN) combined with hypomethylating agents (HMA) in the treatment of higher-risk myelodysplastic syndromes (HR-MDS) and analyze the factors influencing their therapeutic effect.Methods:The clinical data of 83 patients with HR-MDS who were diagnosed at the First Affiliated Hospital of Zhengzhou University between November 2019 and May 2023 were retrospectively analyzed. All patients were treated with VEN combined with HMA. The Kaplan-Meier method was used to depict the survival curves, and the log-rank test was used to compare survival between the groups.Results:The median age was 57 (15-82) years old, and 51 patients (61.4%) were male. Forty-five patients (54.2%) were initially treated with HMA, 23 (27.7%) received ≤4 cycles of HMA, and 15 (18.1%) demonstrated HMA failure. At the median follow-up of 10.3 (0.6-34.4) months, the overall response rate (ORR) was 62.7% (52/83), including 18 patients (21.7%) with a complete response (CR), 14 (16.9%) with a bone marrow CR (mCR) with hematological improvement, and 20 (24.1%) with a mCR. The ORR of patients with initial treatment, ≤4 HMA cycles, and HMA failure were 66.7%, 60.9%, and 53.3%, respectively ( P=0.641). The median overall survival time was 14.6 (95% CI 7.2-22.0) months, and the median progression-free survival time was 8.9 (95% CI 6.7-11.1) months. The multivariate analysis showed that serum alkaline phosphatase (ALP) ≥90 U/L (OR=14.574, 95% CI 3.036-69.951, P=0.001), TP53 mutation ( OR=13.052, 95% CI 1.982-85.932, P=0.008), and U2AF1 mutation ( OR=7.720, 95% CI 1.540-38.698, P=0.013) were independent risk factors for poor efficacy of VEN combined with HMA. Hematological toxicity occurred in all patients, and the incidence of treatment-induced grade 3-4 leukopenia was 48.2% (40/83). Infection was the most common non-hematological adverse event, mainly pulmonary infection (31.3%) . Conclusion:VEN combined with HMA had a high response rate in patients with HR-MDS, both at initial treatment and with HMA failure. ALP ≥ 90 U/L, TP53 mutation, and U2AF1 mutation were independent risk factors for non-response to treatment.

Objective:To study the therapeutic effect of cardiac rehabilitation in patients with acute myocardial infarction(AMI)after percutaneous coronary intervention(PCI)and its effect on inflammatory factors.Methods:A total of 94 AMI patients after PCI admitted in Hospital of China University of Geosciences(Wuhan)between June 2020 and August 2021 were selected and randomly divided into control group(n=47,routine therapy)and study group(n=47,individualized cardiac rehabilitation therapy based on routine therapy).Cardiopulmonary exercise indexes,blood lipid indexes,inflamma-tory factors and cardiac function indexes were compared between two groups before and 3 months after treatment.Results:Compared with control group after treatment,participants in study group had significant higher anaerobic threshold[(15.46±3.07)ml·min-1·kg-1 vs.(19.37±3.27)ml·min 1·kg-1],maximal oxygen uptake[(21.26±4.05)ml·min-1·kg-1 vs.(25.31±4.10)ml·min-1·kg-1],left ventricular ejection fraction(LVEF)[(52.20±5.75)％vs.(57.91±5.17)％],6min walking distance(6MWD)[(430.58±43.87)m vs.(481.52±44.57)m]and levels of high density lipoprotein cholesterol(HDL-C)[(1.30±0.32)mmol/L vs.(1.49±0.35)mmol/L]and interleukin(IL)-10[(5.45±0.55)pg/ml vs.(6.19±0.59)pg/ml](P＜0.01 all),and significant lower levels of triglyceride(TG)[(1.88±0.65)mmol/L vs.(1.54±0.63)mmol/L],total cholesterol(TC)[(3.49±0.54)mmol/L vs.(3.13±0.47)mmol/L],low density lipoprotein cholesterol(LDL-C)[(2.12±0.59)mmol/L vs.(1.57±0.52)mmol/L],tumor necrosis factor-α(TNF-α)[(128.34±14.5)pg/ml vs.(99.28±8.51)pg/ml],leptin(LEP)[(623.49±61.27)pg/ml vs.(483.57±47.61)pg/ml]and N terminal pro B-type natriuretic peptide(NT-proBNP)[(396.59±18.12)pg/ml vs.(302.96±17.56)pg/ml](P＜0.05 or＜0.01).Conclusion:Cardiac rehabilitation therapy can significantly im-prove the blood lipid levels,cardiac function and exercise endurance,and effectively reduce the levels of inflammatory fac-tors in AMI patients after PCI,which is an important component of secondary prevention in these patients.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.