1.Study on the role of oleuropein in enhancing muscle endurance
Huan LI ; Zhen ZHANG ; Jiayi FENG ; Weidong ZHANG ; Xia LIU
Journal of Pharmaceutical Practice and Service 2026;44(3):126-131
Objective Orosomucoid1 (ORM1) is a novel target in the quest for anti-fatigue pharmacotherapy. Preliminary investigations have illuminated oleuropein (OLE) as a promising candidate molecule, poised to enhance ORM1 expression. To elucidate the influence of OLE on ORM1 protein expression and assess its ramifications on muscle endurance. Methods The impact of OLE on ORM1 protein expressions within hepatocytes and liver tissue was meticulously quantified through Western blotting; the effects of OLE on muscle endurance were evaluated via the rotarod and forced swimming tests; glycogen content within liver and muscle tissues was determined utilizing a specialized kit; and PAS staining was employed to visualize glycogen deposition in the gastrocnemius muscle. Results OLE demonstrated a capacity to elevate ORM1 protein expression in hepatocytes in a time- and dose-dependent manner, concurrently prolonging the duration of swimming and rotarod performance in mice, also in a time- and dose-dependent manner. Furthermore, OLE augmented ORM1 expression in liver tissue, elevated serum ORM1 levels, and enhanced glycogen reserves within the liver and muscle. Conclusion OLE may serve to amplify muscle endurance by elevating ORM1 levels in vivo and augmenting glycogen stores within skeletal muscle.
2.Association of traditional Chinese medicine syndromes with blood lipid profiles and cardiovascular prognosis in post-percutaneous coronary intervention atherosclerotic cardiovascular disease patients: a prospective cohort study
Huangyu XU ; Qian LI ; Haozhe XIONG ; Weidong HONG ; Xinyi ZHOU ; Xiaoyan LU ; Xiaoli LIU ; Xinrong FAN
Digital Chinese Medicine 2026;9(1):91-102
Objective:
Patients with atherosclerotic cardiovascular disease (ASCVD) following percutaneous coronary intervention (PCI) are classified as very-high-risk individuals in cardiovascular disease (CVD) risk stratification. The distribution pattern of traditional Chinese medicine (TCM) syndromes in this patient population, as well as its association with blood lipid profiles and clinical prognosis, remains unclear. The present prospective cohort study aims to investigate these correlations, thereby providing insights to enrich the research fields.
Methods:
We enrolled consecutive patients with ASCVD who underwent PCI at the Integrated Cardiology Unit of China-Japan Friendship Hospital between September 1, 2020 and December 31, 2022. Demographics and clinical characteristics, signs and symptoms defining each TCM syndrome, and fasting venous blood samples were collected at baseline and follow up or upon major adverse cardiovascular events (MACEs). We analyzed the correlation between TCM syndromes, blood lipid profiles, and MACEs, and developed a new joint prognostic model incorporating both TCM syndromes and blood lipids using logistic regression. The analyses were based on detailed baseline and one-year follow-up data.
Results:
A per-protocol analysis was performed on 586 patients with complete data ultimately. During the one-year follow-up, 174 patients (29.69%) experienced a MACE. We performed statistical analyses on comorbidities, medication, and biochemical indicators across groups defined by TCM syndrome differentiation. When comparing different TCM syndromes, no significant differences were found in age, body mass index (BMI), history of revascularization, comorbidities, family history of CVD, smoking or drinking, or statin intensity (P > 0.05). Patients with intertwined phlegm and blood stasis syndrome exhibited significantly higher levels of total cholesterol (TC, 5.27 ± 1.18 mmol/L, P < 0.001), triglyceride (TG, 1.96 ± 1.33 mmol/L, P = 0.008), low-density lipoprotein cholesterol (LDL-C, 3.35 ± 0.79 mmol/L, P < 0.001), and high-density lipoprotein cholesterol (HDL-C, 1.24 ± 0.81 mmol/L, P < 0.001) compared with those with other TCM syndromes combined. A multivariable logistic regression model was constructed to predict MACEs. The model included TCM syndrome type [with intertwined phlegm and blood stasis as a predictor, adjusted odds ratio (OR) = 1.413, 95% confidence interval (CI): 0.517 – 3.864, P = 0.501], age (adjusted OR = 0.97, 95% CI: 0.955 – 1.001, P = 0.057), male gender (adjusted OR = 0.698, 95% CI: 0.416 – 1.170, P = 0.173), TC (adjusted OR = 1.004, 95% CI: 0.513 – 1.965, P = 0.990), and LDL-C (adjusted OR = 5.825, 95% CI: 2.214 – 15.326, P < 0.001). This model demonstrated good discriminatory ability for MACEs in post-PCI ASCVD patients [the area under the receiver operating characteristic (ROC) curve (AUC) = 0.865, 95% CI: 0.816 – 0.914].
Conclusion
The intertwined phlegm and blood stasis TCM syndrome is associated with a distinct atherogenic lipid profile characterized by elevated levels of TC and LDL-C. The prognostic model that incorporates this TCM syndrome type along with conventional lipid parameters (TC and LDL-C) shows good discriminatory ability for predicting MACEs in ASCVD patients after PCI, underscoring the potential clinical utility of integrating TCM syndrome differentiation into CVD risk assessment.
3.Thrombus Migration After Tenecteplase Versus Alteplase in Acute Large Vessel Occlusion
Lu WANG ; Fuxia YANG ; Xiao WU ; Lulan LI ; Xueqiao JIAO ; Fangfang ZHANG ; Fengyuan CHE ; Hongxing HAN ; Weidong LIU ; Peifu WANG ; Xuesong LI ; Junfeng SHI ; Jia LIU ; Xunming JI ; Xiuhai GUO
Journal of Stroke 2026;28(2):283-292
Background:
and Purpose In patients with large vessel occlusion (LVO), intravenous thrombolysis (IVT) frequently alters thrombus location; however, the clinical impact of this phenomenon remains unclear. We aimed to compare post-IVT thrombus dynamics between tenecteplase and alteplase and to evaluate the association between thrombus dynamics and 3-month outcomes.
Methods:
This retrospective study analyzed prospectively collected, multicenter data from consecutive patients with LVO who underwent bridging therapy between January 2022 and December 2024. Thrombus dynamics were classified as resolution, migration, or stability. Analyses incorporated propensity score matching with weighting to balance baseline characteristics.
Results:
Of the 806 initially included patients, 746 were included after matching (373 treated with tenecteplase and 373 treated with alteplase). The incidence of thrombus migration was significantly higher in the tenecteplase group than in the alteplase group (19.3% vs. 11.3%; odds ratio [OR]: 1.92; 95% confidence interval [CI] 1.27–2.91). The advantage of tenecteplase over alteplase was restricted to patients with an IVT-to-puncture time of <60 minutes (18.6% vs. 6.2%; p=0.001) and was no longer significant when the interval ≥60 minutes (19.7% vs. 15.0%; p=0.204; pinteraction=0.043). Additionally, thrombus migration was associated with a better functional outcome (OR: 1.62; 95% CI 1.04–2.53). Finally, tenecteplase was associated with improved functional independence compared with alteplase (OR: 1.43; 95% CI 1.04–1.95).
Conclusions
Tenecteplase demonstrated superior efficacy in inducing thrombus migration compared with alteplase, particularly within 60 minutes of IVT administration. Thrombus migration independently predicted improved functional independence. These findings support the preferential use of tenecteplase for bridging therapy in patients with LVO.
4.Investigation of Specific Antibody Levels of Autoimmune Gastritis and Analysis of Influencing Factors in A Community Population in Xinjiang
Huan LIU ; Xiaoling HUANG ; AI HEMAIJIANG KURBANJIANG ; Yan FENG ; Weidong LIU ; Shenglong XUE ; Zequan XIAO ; AINI ABDUREIM ; Xinwen GUO ; Maosen JIANG ; Feng GAO
Medical Journal of Peking Union Medical College Hospital 2026;17(4):1042-1050
To investigate the positivity rates of specific antibodies, including parietal cell antibody (PCA) and anti-inner factor antibody (IFA), in a community population in Xinjiang for autoimmune gastritis (AIG), determine the prevalence of AIG, and analyze the correlations of PCA and IFA with clinical characteristics, pepsinogen (PG), gastrin 17 (G17), and A cross-sectional survey was conducted using stratified random cluster sampling in community populations across 10 regions of Xinjiang from January 2022 to December 2023. General information was collected via a self-designed questionnaire, and fasting venous blood samples were obtained to measure laboratory parameters including PCA, IFA, PG Ⅰ, PG Ⅱ, PG Ⅰ/PG Ⅱ ratio, and G17. The positivity rates of PCA and IFA and the prevalence of AIG were calculated. Spearman correlation analysis was used to assess the relationships of PCA and IFA with PG Ⅰ, PG Ⅱ, PG Ⅰ/PG Ⅱ ratio, and G17. The diagnostic efficacy of PCA and IFA for atrophic gastritis was evaluated using receiver operating characteristic (ROC) curves, and multivariate logistic regression analysis was performed to identify factors influencing PCA and IFA positivity. A total of 2018 community participants were included, comprising 972 males (48.17%) and 1046 females (51.83%), with a mean age of 42±19 years. The predominant ethnic groups were Han (42.22%) and Kazakh (33.10%). Hp-Ab positivity was observed in 1244 cases (61.65%). Serological criteria for atrophic gastritis were met in 56 cases (2.78%). PCA positivity was found in 253 cases (12.54%), IFA positivity in 30 cases (1.49%), and dual positivity in 11 cases (0.55%). A total of 617 participants (30.57%) voluntarily underwent endoscopic examination, among whom 7 cases (1.13%) were histopathologically confirmed as AIG. Positivity rates for PCA and IFA varied among ethnic groups, with the highest rates observed in the Kirgiz population (23.53% and 5.88%, respectively). Spearman correlation analysis revealed that PCA was negatively correlated with the PG Ⅰ/PG Ⅱ ratio ( The positivity rate of PCA is relatively high in the community population in Xinjiang and varies across different ethnic groups, whereas the positivity rate of IFA is lower than that of PCA. Age, history of alcohol consumption, history of allergies, and history of thyroid disease are associated with PCA positivity, while no correlation was found between Hp-Ab and PCA or IFA. The prevalence of histopathologically confirmed AIG among participants undergoing endoscopic examination is 1.13%.
5.Guidelines for the perioperative diagnosis and treatment of oncogene-driven non-small cell lung cancer (2026)
Weidong WANG ; Yongbin LIN ; Hui TIAN ; Gaofeng LI ; Shun XU ; Yongde LIAO ; Haitao MA ; Junfeng LIU ; Chundong GU ; Xiaolong YAN ; Shumin WANG ; Daqiang SUN ; Jianyang LIU ; Tao XUE ; Shaohua MA ; Zhigang LI ; Shuanghu YUAN ; Gen LIN ; Ling CAI ; Jianping ZHOU ; Wenzhao ZHONG ; Naixin LIANG ; Yi HAN ; Junfeng WANG ; Weidong ZHANG ; Xin WANG ; Lianjuan CHEN ; Lunxu LIU ; Xiuyi ZHI ; Lanjun ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(09):1337-1353
Lung cancer constitutes the most prevalent and lethal malignant tumor in China. Approximately 85% of lung cancer diagnoses correspond to the non-small cell histological subtype [non-small cell lung cancer (NSCLC)]. Despite surgery being the mainstay for early-stage disease, postoperative recurrence remains high and adjuvant chemotherapy offers limited benefit. In recent years, targeted therapy has demonstrated substantial advantages in driver mutation-positive NSCLC. To this end, the Lung Cancer Medical Education Committee of the Chinese Medical Education Association developed guidelines based on a systematic review of evidence through November 2025, using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach and a modified Delphi method. Focusing on epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and addressing ROS proto-oncogene 1 (ROS1), B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E mutation, and mesenchymal-epithelial transition factor (MET) exon 14 (METex14) skipping, the guideline covers molecular testing, neoadjuvant/adjuvant therapy, perioperative strategies, minimal residual disease monitoring, and postoperative surveillance. It defines testing requirements, specifies stage-directed and subtype-specific treatments, and standardizes minimal residual disease monitoring. These recommendations emphasize precision and feasibility to improve survival and quality of life.
6.Clinical Randomized Controlled Trial of Traditional Chinese Medicine Compound Shenlong Decoction Granules in Treatment of Idiopathic Pulmonary Fibrosis
Qi SI ; Ningzi ZANG ; Mei WANG ; Weidong ZHENG ; Chuang LIU ; Yongming LIU ; Haoyang ZHANG ; Zhongxue ZHAO ; Jiyu ZOU ; Jingze LI ; Lijian PANG ; Xiaodong LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):237-245
ObjectiveTo assess the therapeutic effectiveness and safety of the traditional Chinese medicine compound Shenlong decoction in addressing the symptoms of pulmonary deficiency and stasis in patients with idiopathic pulmonary fibrosis (IPF). MethodsSixty eligible patients with lung deficiency and collateral stasis syndrome of IPF were randomly assigned to the observation (30 patients) and control groups (30 patients). All patients underwent standard Western medical therapy. Additionally,the observation group received Shenlong decoction granules,while the control group received a placebo. Both treatments were packaged in four doses of 10.5 g each,taken twice daily for three months. The indexes of the patients during the treatment cycle were observed,and the main indexes include traditional Chinese medicine (TCM) syndrome scores and 6 min walk test (6MWT). The secondary indexes include pulmonary function test [actual value/expected value of total lung volume (TLC%),actual value/expected value of vital capacity(FVC%),actual/predicted diffusing capacity of the lung for carbon monoxide(DLCO%),actual/predicted forced expiratory volume in one second (FEV1%),and FEV1/ forced vital capacity (FVC)],blood gas analysis [arterial blood diathesis partial pressure of oxygen (PaO2),partial pressure of carbon dioxide (PaCO2),and arterial oxygen saturation (SaO2)],serum inflammatory factors [transforming growth factor-β1 (TGF-β1),interleukin-4 (IL-4),interleukin-13 (IL-13),interleukin-12 (IL-12),and gamma-interferon (IFN-γ)],and quality of survival evaluation [St George's Respiratory Questionnaire (SGRQ) score]. The patients' clinical manifestations were determined at the end of the treatment, and the occurrence of adverse events was recorded. ResultsA total of 53 patients completed the study,comprising 27 in the control group and 26 in the observation group. Upon completion of the treatment period,the control group achieved a total effective rate of 33.33% (9/27),whereas the observation group demonstrated a total effective rate of 53.85% (14/26),which was statistically superior to the control group (χ2=4.034,P<0.05). After the treatment,the TCM syndrome scores,6MWT,DLCO%,FEV1%,PaO2,PaCO2,TGF-β1,IL-4,IL-13,IL-12,and IFN-γ in the two groups were all significantly improved (P<0.01). Compared with those in the control group after treatment at the same period,the TCM syndrome scores,6MWT,PaO2,and PaCO2 were significantly improved in the observation group after 60 days and 90 days of medication (P<0.01). Three months after the end of medication,the SGRQ score in the observation group showed significant improvement when compared to that in the control group (P<0.05),and no severe adverse events were reported during the follow-up period. ConclusionCompound Shenlong decoction can alleviate clinical symptoms such as shortness of breath and wheezing in patients with lung deficiency and collateral stasis syndrome of IPF,enhance exercise tolerance,improve the quality of life,and have certain potential advantages in improving pulmonary function.
7.Clinical Randomized Controlled Trial of Traditional Chinese Medicine Compound Shenlong Decoction Granules in Treatment of Idiopathic Pulmonary Fibrosis
Qi SI ; Ningzi ZANG ; Mei WANG ; Weidong ZHENG ; Chuang LIU ; Yongming LIU ; Haoyang ZHANG ; Zhongxue ZHAO ; Jiyu ZOU ; Jingze LI ; Lijian PANG ; Xiaodong LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):237-245
ObjectiveTo assess the therapeutic effectiveness and safety of the traditional Chinese medicine compound Shenlong decoction in addressing the symptoms of pulmonary deficiency and stasis in patients with idiopathic pulmonary fibrosis (IPF). MethodsSixty eligible patients with lung deficiency and collateral stasis syndrome of IPF were randomly assigned to the observation (30 patients) and control groups (30 patients). All patients underwent standard Western medical therapy. Additionally,the observation group received Shenlong decoction granules,while the control group received a placebo. Both treatments were packaged in four doses of 10.5 g each,taken twice daily for three months. The indexes of the patients during the treatment cycle were observed,and the main indexes include traditional Chinese medicine (TCM) syndrome scores and 6 min walk test (6MWT). The secondary indexes include pulmonary function test [actual value/expected value of total lung volume (TLC%),actual value/expected value of vital capacity(FVC%),actual/predicted diffusing capacity of the lung for carbon monoxide(DLCO%),actual/predicted forced expiratory volume in one second (FEV1%),and FEV1/ forced vital capacity (FVC)],blood gas analysis [arterial blood diathesis partial pressure of oxygen (PaO2),partial pressure of carbon dioxide (PaCO2),and arterial oxygen saturation (SaO2)],serum inflammatory factors [transforming growth factor-β1 (TGF-β1),interleukin-4 (IL-4),interleukin-13 (IL-13),interleukin-12 (IL-12),and gamma-interferon (IFN-γ)],and quality of survival evaluation [St George's Respiratory Questionnaire (SGRQ) score]. The patients' clinical manifestations were determined at the end of the treatment, and the occurrence of adverse events was recorded. ResultsA total of 53 patients completed the study,comprising 27 in the control group and 26 in the observation group. Upon completion of the treatment period,the control group achieved a total effective rate of 33.33% (9/27),whereas the observation group demonstrated a total effective rate of 53.85% (14/26),which was statistically superior to the control group (χ2=4.034,P<0.05). After the treatment,the TCM syndrome scores,6MWT,DLCO%,FEV1%,PaO2,PaCO2,TGF-β1,IL-4,IL-13,IL-12,and IFN-γ in the two groups were all significantly improved (P<0.01). Compared with those in the control group after treatment at the same period,the TCM syndrome scores,6MWT,PaO2,and PaCO2 were significantly improved in the observation group after 60 days and 90 days of medication (P<0.01). Three months after the end of medication,the SGRQ score in the observation group showed significant improvement when compared to that in the control group (P<0.05),and no severe adverse events were reported during the follow-up period. ConclusionCompound Shenlong decoction can alleviate clinical symptoms such as shortness of breath and wheezing in patients with lung deficiency and collateral stasis syndrome of IPF,enhance exercise tolerance,improve the quality of life,and have certain potential advantages in improving pulmonary function.
8.Effect of mild hypercapnia during the recovery period on the emergence time from total intravenous anesthesia: a randomized controlled trial
Lan LIU ; Xiangde CHEN ; Qingjuan CHEN ; Xiuyi LU ; Lili FANG ; Jinxuan REN ; Yue MING ; Dawei SUN ; Pei CHEN ; Weidong WU ; Lina YU
Korean Journal of Anesthesiology 2025;78(3):215-223
Background:
Intraoperative hypercapnia reduces the time to emergence from volatile anesthetics, but few clinical studies have explored the effect of hypercapnia on the emergence time from intravenous (IV) anesthesia. We investigated the effect of inducing mild hypercapnia during the recovery period on the emergence time after total IV anesthesia (TIVA).
Methods:
Adult patients undergoing transurethral lithotripsy under TIVA were randomly allocated to normocapnia group (end-tidal carbon dioxide [ETCO2] 35–40 mmHg) or mild hypercapnia group (ETCO2 50-55 mmHg) during the recovery period. The primary outcome was the extubation time. The spontaneous breathing-onset time, voluntary eye-opening time, and hemodynamic data were collected. Changes in the cerebral blood flow velocity in the middle cerebral artery were assessed using transcranial Doppler ultrasound.
Results:
In total, 164 patients completed the study. The extubation time was significantly shorter in the mild hypercapnia (13.9 ± 5.9 min, P = 0.024) than in the normocapnia group (16.3 ± 7.6 min). A similar reduction was observed in spontaneous breathing-onset time (P = 0.021) and voluntary eye-opening time (P = 0.008). Multiple linear regression analysis revealed that the adjusted ETCO2 level was a negative predictor of extubation time. Middle cerebral artery blood flow velocity was significantly increased after ETCO2 adjustment for mild hypercapnia, which rapidly returned to baseline, without any adverse reactions, within 20 min after extubation.
Conclusions
Mild hypercapnia during the recovery period significantly reduces the extubation time after TIVA. Increased ETCO2 levels can potentially enhance rapid recovery from IV anesthesia.
9.Effect of mild hypercapnia during the recovery period on the emergence time from total intravenous anesthesia: a randomized controlled trial
Lan LIU ; Xiangde CHEN ; Qingjuan CHEN ; Xiuyi LU ; Lili FANG ; Jinxuan REN ; Yue MING ; Dawei SUN ; Pei CHEN ; Weidong WU ; Lina YU
Korean Journal of Anesthesiology 2025;78(3):215-223
Background:
Intraoperative hypercapnia reduces the time to emergence from volatile anesthetics, but few clinical studies have explored the effect of hypercapnia on the emergence time from intravenous (IV) anesthesia. We investigated the effect of inducing mild hypercapnia during the recovery period on the emergence time after total IV anesthesia (TIVA).
Methods:
Adult patients undergoing transurethral lithotripsy under TIVA were randomly allocated to normocapnia group (end-tidal carbon dioxide [ETCO2] 35–40 mmHg) or mild hypercapnia group (ETCO2 50-55 mmHg) during the recovery period. The primary outcome was the extubation time. The spontaneous breathing-onset time, voluntary eye-opening time, and hemodynamic data were collected. Changes in the cerebral blood flow velocity in the middle cerebral artery were assessed using transcranial Doppler ultrasound.
Results:
In total, 164 patients completed the study. The extubation time was significantly shorter in the mild hypercapnia (13.9 ± 5.9 min, P = 0.024) than in the normocapnia group (16.3 ± 7.6 min). A similar reduction was observed in spontaneous breathing-onset time (P = 0.021) and voluntary eye-opening time (P = 0.008). Multiple linear regression analysis revealed that the adjusted ETCO2 level was a negative predictor of extubation time. Middle cerebral artery blood flow velocity was significantly increased after ETCO2 adjustment for mild hypercapnia, which rapidly returned to baseline, without any adverse reactions, within 20 min after extubation.
Conclusions
Mild hypercapnia during the recovery period significantly reduces the extubation time after TIVA. Increased ETCO2 levels can potentially enhance rapid recovery from IV anesthesia.
10.Effect of mild hypercapnia during the recovery period on the emergence time from total intravenous anesthesia: a randomized controlled trial
Lan LIU ; Xiangde CHEN ; Qingjuan CHEN ; Xiuyi LU ; Lili FANG ; Jinxuan REN ; Yue MING ; Dawei SUN ; Pei CHEN ; Weidong WU ; Lina YU
Korean Journal of Anesthesiology 2025;78(3):215-223
Background:
Intraoperative hypercapnia reduces the time to emergence from volatile anesthetics, but few clinical studies have explored the effect of hypercapnia on the emergence time from intravenous (IV) anesthesia. We investigated the effect of inducing mild hypercapnia during the recovery period on the emergence time after total IV anesthesia (TIVA).
Methods:
Adult patients undergoing transurethral lithotripsy under TIVA were randomly allocated to normocapnia group (end-tidal carbon dioxide [ETCO2] 35–40 mmHg) or mild hypercapnia group (ETCO2 50-55 mmHg) during the recovery period. The primary outcome was the extubation time. The spontaneous breathing-onset time, voluntary eye-opening time, and hemodynamic data were collected. Changes in the cerebral blood flow velocity in the middle cerebral artery were assessed using transcranial Doppler ultrasound.
Results:
In total, 164 patients completed the study. The extubation time was significantly shorter in the mild hypercapnia (13.9 ± 5.9 min, P = 0.024) than in the normocapnia group (16.3 ± 7.6 min). A similar reduction was observed in spontaneous breathing-onset time (P = 0.021) and voluntary eye-opening time (P = 0.008). Multiple linear regression analysis revealed that the adjusted ETCO2 level was a negative predictor of extubation time. Middle cerebral artery blood flow velocity was significantly increased after ETCO2 adjustment for mild hypercapnia, which rapidly returned to baseline, without any adverse reactions, within 20 min after extubation.
Conclusions
Mild hypercapnia during the recovery period significantly reduces the extubation time after TIVA. Increased ETCO2 levels can potentially enhance rapid recovery from IV anesthesia.

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