ObjectiveTo observe the effects of Xiaoyaosan on glucagon-like peptide-1 （GLP-1）/GLP-1 receptor （GLP-1r） and protein kinase A （PKA）/cAMP response element binding protein （CREB）/brain-derived neurotrophic factor （BDNF） signaling pathways in the hippocampal CA1 region of rats under chronic restraint stress （CRS），and to explore the mechanism of this formula to alleviate anxiety and depression-like behaviors. Methods40 specific pathogen-free male Sprague-Dawley （SD） rats were randomly divided into normal，model，Xiaoyaosan，and fluoxetine groups，with 10 rats in each group. CRS was used to induce anxiety and depression-like behaviors. The rats in the Xiaoyaosan group were gavaged with aqueous solution of traditional Chinese medicine formula granules （7.36 g·kg^-1·d^-1），while those in the fluoxetine group were gavaged with aqueous solution of fluoxetine （2 mg·kg^-1·d^-1）. Body weight was measured on days 0，7，14，and 21 of the experiment. On days 0 and 22 of the experiment，the sucrose preference test （SPT），forced swimming test （FST），and open field test （OFT） were performed. The pathological morphology of the hippocampal CA1 region was observed by Nissl staining. The relative mRNA expression of post-synaptic density protein-95 （PSD95） and synapsin （SYP） was detected by reverse transcription quantitative real-time polymerase chain reaction. Immunohistochemistry and Western blot were used to detect expression of proteins in the GLP-1/GLP-1r and PKA/CREB/BDNF pathways in the hippocampal CA1 region. ResultsAfter CRS modeling，compared with the normal group，the rats of the model group had anxiety and depression-like behavioral manifestations，neuronal damage in the hippocampal CA1 region，significantly downregulated expression of synaptic plasticity markers PSD95 and SYP genes （P<0.01），and inhibition of GLP-1/GLP-1r and PKA/CREB/BDNF signaling pathways （P<0.05，P<0.01）. Compared with the model group，the Xiaoyaosan group exhibited alleviated anxiety and depression-like behaviors，reduced neuronal damage in the hippocampal CA1 region， significantly increased expression of PSD95 and SYP genes （P<0.01），and the activation of the GLP-1/GLP-1r and PKA/CREB/BDNF signaling pathways （P<0.05，P<0.01）. ConclusionXiaoyaosan can alleviate anxiety and depression-like behaviors in CRS rats by improving synaptic plasticity in the hippocampal CA1 region. The mechanisms may be related to the activation of the GLP-1/GLP-1r pathway and its mediated PKA/CREB/BDNF signaling pathway by the formula.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

ObjectiveTo observe the effect of Shengxiantang （SXT） on cell senescence mediated by wingless/integrated （Wnt）3a/β-catenin pathway in rats with idiopathic pulmonary fibrosis （IPF） and reveal the possible mechanism in improving lung function of IPF rats. MethodA total of 32 SPF level SD rats were randomly divided into sham group， model group， pirfenidone group， and SXT group. The IPF rat model was established by intratracheal instillation of bleomycin （0.005 g·kg^-1）. The following day after surgery， rats in the SXT group were given the aqueous solution of SXT granules （0.78 g·kg^-1）， and the pirfenidone group was given pirfenidone suspension （0.05 g·kg^-1）. The other groups were given deionized water （10 mL·kg^-1） for 28 consecutive days. Lung tissue was collected after the lung function was measured. The pathological changes of the lung tissue were observed by hematoxylin-eosin （HE） and Masson staining， and then the Szapiel score and Ashcroft score were performed. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect telomere length. Western blot was applied to detect the expressions of epithelial-mesenchymal transformation （EMT） markers ［α-smooth muscle actin （α-SMA） and E-cadherin］， telomere reverse transcriptase （TRET）， aging-related proteins （p53 and p21）， senescence-associated secretory phenotype ［interleukin-6 （IL-6） and matrix metalloproteinase-1 （MMP-1）］， and key proteins of Wnt signaling pathway ［Wnt3a， glycogen synthase kinase-3β （GSK-3β）， β-catenin， Cyclin D₁， and c-Myc］. ResultCompared with those in the Sham group， peak expiratory flow （PEF） and minute ventilation volume （MV） in the model group were significantly decreased （P<0.01）， and the frequency of respiratory （f） was significantly increased （P<0.01）. The Szapiel score， Ashcroft score， and protein expression of α-SMA， p53， p21， IL-6， MMP-1， Wnt3a， GSK3β， β-catenin， Cyclin D₁， and c-Myc were increased （P<0.01）. The expressions of E-cadherin and TERT， as well as telomere length were significantly decreased （P<0.01）. Compared with those in the model group， PEF and MV in the SXT group were significantly increased （P<0.01）， while f was significantly decreased （P<0.01）. The Szapiel score， Ashcroft score， and protein expression of α-SMA， p53， p21， IL-6， MMP-1， Wnt3a， GSK3β， β-catenin， Cyclin D₁， and c-Myc were significantly decreased （P<0.05， P<0.01）. Nevertheless， the expression of E-cadherin and TERT， as well as telomere length were significantly increased （P<0.01）. ConclusionSXT presents a significant protective effect on lung function in IPF rats， and the prescription may act on the Wnt3a/β-catenin signaling pathway to regulate cell senescence induced by TERT to inhibit EMT.

OBJECTIVE To evaluate the cost-effectiveness of trastuzumab deruxtecan（T-DXd） versus trastuzumab emtansine （T-DM1） in the second-line treatment of HER2-positive metastatic breast cancer， and to provide a basis for the selection of clinical medication regimen and medical and health decisions. METHODS Based on the clinical trial DESTINY-Breast03， a partitioned survival model was constructed， with a cycle of 3 weeks as the simulation of patients’ lifetime. The incremental cost-effectiveness ratio （ICER） was calculated by using quality-adjusted life years （QALY） as output indicators， and sensitivity analysis was used to verify the robustness of the basic analysis results； the cost-effectiveness of the second-line treatment for HER2-positive metastatic breast cancer was compared between T-DXd and T-DM1. RESULTS Under the premise of taking 3 times China’s per capita gross domestic product （GDP） in 2022 as the willingness-to-pay threshold （257 094 yuan/QALY）， the T-DXd group also needed to pay more cost compared with T-DM1 group while obtaining incremental utility （0.69 QALYs）， and the ICER value was 1 850 478.40 yuan/QALY. The results of univariate sensitivity analysis showed that progression-free survival state utility value， T-DXd price， cost discount rate were factors that had a great influence on ICER value， but these parameters could not flip the basic analysis results within a reasonable range. In the probability sensitivity analysis， when the threshold of willingness-to-pay rose to 1 500 400 yuan/QALY， the probability of economic activity was 50% in the T-DXd regimen. The results of the scenario analysis also verified the robustness of the original research results. CONCLUSIONS Under the premise of 3 times China’s per capita GDP as the WTP threshold， compared with T-DM1， T-DXd is not cost-effective in the second-line treatment of HER2-positive metastatic breast cancer.

Objective:To investigate the efficacy of robot-assisted femoral tunnel localization in reconstruction of the medial patellofemoral ligament (MPFL).Methods:A retrospective study was conducted to analyze the 36 patients who had been admitted to Department of Sports Medicine, The Fourth Hospital of Wuhan between January 2019 and January 2022 due to recurrent patellar dislocation. There were 15 males and 21 females; age: 23.5 (18.3, 29.0) years; number of dislocations: 2.5 (2.0, 3.0). They were stratified into 2 cohorts based on utilization of robot-assistance. In the observation group (17 cases), the femoral tunnel localization was robot-assisted in MPFL reconstruction; in the control group (19 cases), the femoral tunnel localization was guided by C-arm fluoroscopy in MPFL reconstruction. The 2 groups were compared in terms of operation time, frequency of guide wire placement, visual analogue scale (VAS) at postoperative 1 d, patellar tilt angle (PTA) and the disparity between actual femoral tunnel insertion and ideal tunnel insertion point (Sch?ttle point) at postoperative 1 to 3 d, and Lysholm knee score and International Knee Documentation Committee (IKDC) score at the last follow-up.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). All patients were followed up for 12.0 (10.3, 13.0) months. In the observation group, the operation time [(64.1±16.7) min], frequency of guide wire placement [1.0 (1.0, 2.0) times], VAS [2.5 (2.0, 3.0) points], and disparity between actual femoral tunnel insertion and ideal tunnel insertion point [(4.7±1.2) mm] were significantly better than those in the control group [(84.2±19.7) min, 3.0 (2.0, 4.0) times, 3.5 (3.0, 4.0) points, and (6.1±1.2) mm] ( P<0.05). There was no statistical difference between the 2 groups in PTA, Lysholm knee score or IKDC score ( P>0.05). Conclusions:The short-term clinical efficacy of robot-assisted femoral tunnel localization is satisfactory in MPFL reconstruction. Compared with the intraoperative C-arm fluoroscopy, robot-assisted localization can decrease the frequency of guide wire placement, enhance femoral tunnel accuracy and efficiency, and alleviate more postoperative pain for the patients.

It is believed that retention due to deficient qi is an important pathogenesis of endometriosis （EMs）. Deficient qi is the root of the disease， mainly manifested as spleen deficiency， while retention is the branch pathogenesis of the disease， mainly with blood stasis， complicated with constraint， phlegm， heat， toxin and other pathological factors. Therefore， it is proposed to follow the treatment principle of supplementing deficiency and unblocking stagnation， and take the methods of replenishing qi and fortifying the spleen， removing stasis and eliminating concretions. Self-made Fuzheng Huayu Formula （扶正化瘀方） is taken as the basic formula， and can be modified with the symptoms in menstrual and non-menstrual periods. Additionally， the methods of moving qi， dispelling phlegm， clearing heat， relieving toxin and others can be combined， and it is recommended to treat the root and the branch simultaneously.

Objective: To explore the prevalence and related factors of overweight, obesity and hypertension comorbidities among children and adolescents in Ningxia, so as to provide a scientific basis for effective early health intervention in children and adolescents. Methods: From September 2021 to June 2022, a total of 4 577 students aged 9-16 were selected from Jinfeng District of Yinchuan City, Shapotou District of Zhongwei City, Yanchi County of Wuzhong City and Pingluo County of Shizuishan City in Ningxia by multi stage cluster random sampling method for questionnaire survey and physical measurement. The influencing factors of overweight, obesity and hypertension comorbidities in children and adolescents were investigated by Chi square test and multivariate unconditioned Logistic regression analysis with weighted complex sampling design. Results: The prevalence of overweight and obesity among primary and secondary school students in Ningxia was 22.87%, the prevalence of hypertension was 1.30%, and the comorbity rate of overweight, obesity and hypertension was 1.07%. Multivariate Logistic regression analysis showed that students aged 13-16 ( OR =15.66,95% CI =3.84-63.96, P <0.05) were more likely to suffer from overweight, obesity and hypertension than students aged 9-12. The students of insufficient sleep duration ( OR =5.47, 95% CI =1.73-17.33, P <0.05) had higher levels of overweight, obesity and hypertension comorbidities than those of adequate sleep duration. Students who had breakfast 1 to 7 times a week ( OR =0.08, 95% CI =0.02-0.37) had lower incidence than those who had breakfast once a week ( P <0.05). Conclusions Age, sleep time and breakfast frequency are all related factors of overweight, obesity and hypertension co morbidity among primary and secondary school students in Ningxia. Close attention should be paid to students aged 9-12 years with insufficient sleep time and fasting in the morning, and carry out scientific education and prevention and control interventions should be carried out.