Objective To longitudinally investigate the characteristics of postoperative weight changes in patients with esophageal cancer and analyze its influencing factors, which can provide certain guidance for nutritional intervention in patients with esophageal cancer. Methods Patients with esophageal cancer who underwent surgical treatment at the Sichuan Cancer Hospital from December 2020 to February 2022 were prospectively included. The general information questionnaire and body composition analyzer were used to longitudinally investigate the patients’ weight and body composition before surgery (T0), 1 month after surgery (T1), 3 months after surgery (T2) and 6 months after surgery (T3), and the change characteristics were analyzed. The generalized estimating equation was used to analyze the influencing factors for postoperative weight changes in patients with esophageal cancer. Results A total of 130 patients were enrolled, including 110 males and 20 females, aged 42-79 (63.33±8.16) years. The weight and body composition of patients with esophageal cancer showed a continuous slow downward trend within 6 months after surgery. The weight loss rate of patients at 1, 3, and 6 months after surgery was 5.10%, 7.76%, and 9.86%, respectively. The analysis results of the influencing factors for postoperative weight showed that patients with the following characteristics had more weight loss: female (β=−7.703, P=0.001), ≥60 years (β=−3.657, P=0.010), smoking (β=4.622, P=0.010), low tumor differentiation degree (β=4.314, P=0.039), and high frequency of eating (β=−3.400, P=0.008). Conclusion Weight loss is an important health problem for patients with esophageal cancer after surgery, and patients have a continuous downward trend in weight within 6 months after surgery. Medical staff should pay special attention to the patients who are female, ≥60 years, having smoking history and low tumor differentiation degree.

Objective To study anti-inflammatory activities of oridonin derivatives without Michael fragment. Methods Two oridonin sulfonylureas were designed and synthesized by a photocatalysis reaction and a scaffold hopping strategy. The inhibitory rate of IL-1β was selected for anti-inflammatory activity evaluation. Results Both compound ZM658 and ZM659 revealed potent anti-inflammatory activities with the values of 69.3% and 59.7% in THP-1 cells, respectively. Moreover, two compounds also showed dose-dependent and low cytotoxicity. Conclusion The result indicated that Michael receptor fragment of oridonin could be substituted with sulfonylurea group.

BACKGROUND: The effects of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment on coronavirus disease 2019 (COVID-19) patients have been preliminarily characterized. However, real-world data on the safety and efficacy of intravenous transfusions of MSCs in hospitalized COVID-19 patients at the convalescent stage remain to be reported. METHODS: This was a single-arm, multicenter, real-word study in which a contemporaneous external control was included as the control group. Besides, severe and critical COVID-19 patients were considered together as the severe group, given the small number of critical patients. For a total of 110 patients, 21 moderate patients and 31 severe patients were enrolled in the MSC treatment group, while 26 moderate patients and 32 severe patients were enrolled in the control group. All patients received standard treatment. The MSC treatment patients additionally received intravenous infusions of MSCs at a dose of 4 × 10 7 cells on days 0, 3, and 6, respectively. The clinical outcomes, including adverse events (AEs), lung lesion proportion on chest computed tomography, pulmonary function, 6-min walking distance (6-MWD), clinical symptoms, and laboratory parameters, were measured on days 28, 90, 180, 270, and 360 during the follow-up visits. RESULTS: In patients with moderate COVID-19, MSC treatment improved pulmonary function parameters, including forced expiratory volume in the first second (FEV1) and maximum forced vital capacity (VCmax) on days 28 (FEV1, 2.75 [2.35, 3.23] vs . 2.11 [1.96, 2.35], P  = 0.008; VCmax, 2.92 [2.55, 3.60] vs . 2.47 [2.18, 2.68], P  = 0.041), 90 (FEV1, 2.93 [2.63, 3.27] vs . 2.38 [2.24, 2.63], P  = 0.017; VCmax, 3.52 [3.02, 3.80] vs . 2.59 [2.45, 3.15], P  = 0.017), and 360 (FEV1, 2.91 [2.75, 3.18] vs . 2.30 [2.16, 2.70], P  = 0.019; VCmax,3.61 [3.35, 3.97] vs . 2.69 [2.56, 3.23], P  = 0.036) compared with the controls. In addition, in severe patients, MSC treatment notably reduced the proportion of ground-glass lesions in the whole lung volume on day 90 ( P  = 0.045) compared with the controls. No difference in the incidence of AEs was observed between the two groups. Similarly, no significant differences were found in the 6-MWD, D-dimer levels, or interleukin-6 concentrations between the MSC and control groups. CONCLUSIONS: Our results demonstrate the safety and potential of MSC treatment for improved lung lesions and pulmonary function in convalescent COVID-19 patients. However, comprehensive and long-term studies are required to confirm the efficacy of MSC treatment. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR2000031430.
Humans ; COVID-19/therapy* ; Female ; Male ; Mesenchymal Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adult ; Umbilical Cord/cytology* ; Mesenchymal Stem Cells/cytology* ; SARS-CoV-2 ; Aged ; Treatment Outcome

Objective To investigate the role and mechanism of paeoniflorin(PF)in sepsis-associated acute kidney injury(SA-AKI)in mice.Methods Mouse SA-AKI model was constructed by intraperitoneal injection of 15 mg/kg LPS.Twenty-four male C57BL/6J mice(6～8 weeks old,weighing 20～25 g)were randomly divided into Control group,model group,PF group(intraperitoneally injected with 50 mg/kg PF 30 min before LPS administration),and β-catenin specific agonist BML284 group(10 mg/kg BML284 by intraperitoneal injection after 50 mg/kg PF administration).The renal histopathological changes were observed by HE staining and Paller scoring.ELISA was used to determine the contents of serum creatinine(Scr),neutrophil gelatinase-associated lipocalin(NGAL)and lactate,and renal contents of hexokinase 2(HK2),lactate dehydrogenase A(LDHA),IL-1β and IL-18.Western blotting was performed to detect the expression of total β-catenin,p-β-cateninY654,nucleus β-catenin and c-Myc.Results Compared with the Control group,the LPS group showed obviously damaged renal tissue,higher Paller score(P＜0.05),increased serum Scr and NGAL levels(P＜0.05),elevated renal contents of aerobic glycolytic indexes such as HK2,LDHA and serum lactate,as well as contents of IL-1β and IL-18(P＜0.05),and enhanced expression of total β-catenin,p-β-cateninY654,nucleus β-catenin and c-Myc in the renal tissue(P＜0.05).PF treatment attenuated the renal tissue damage,decreased Paller score(P＜0.05),reduced serum Scr and NGAL levels(P＜0.05),HK2,LDHA and serum lactate levels,and contents of IL-1 β and IL-18 in renal tissues(P＜0.05),and down-regulated the renal expression of total β-catenin,p-β-cateninY654,nucleusβ-catenin and c-Myc when compared with the levels in the model group(P＜0.05).While,addition of BML284 reversed above effects of PF treatment with significant differences(P＜0.05).Conclusion PF can alleviate SA-AKI,and its mechanism may be through its inhibiting the β-catenin/c-Myc pathway,thus reducing the aerobic glycolysis level and inflammatory response in renal tissue.

Objective To investigate the effects of paeoniflorin(PF)on lipopolysaccharide(LPS)-induced aerobic glycolysis in renal tubular epithelial cell line HK-2 and its underlying mechanism of action.Methods This study consists of a preliminary experiment and a formal experiment.Preliminary experiment:CCK-8 assay and RT-qPCR were used respectively to measure cell viability and mRNA expression levels of inflammatory factors in HK-2 cells after LPS stimulation to determine the optimal LPS concentration for modeling as well as to evaluate the toxicity of PF and screen for its appropriate concentration.Formal experiment:HK-2 cells were divided into control group(CON group),LPS group,LPS+PF group and LPS+PF+740Y-P group.LPS was used to establish a cell model of sepsis associated-acute kidney injury(SA-AKI)in HK-2 cells,and then the cell model was treated with PF and PI3K activator 740Y-P,correspondingly for 24 h.CCK-8 assay was employed to detect cell viability,and Extracellular Acidification Rate(ECAR)Kit was utilized to measure the rate.The contents of IL-1β,IL-18,lactic acid(Lac)and lactate dehydrogenase A(LDHA)were determined with ELISA.Western blotting was applied to detect the expression of p-PI3K,p-AKT,HIF-1α,pyruvate kinase 2(PKM2,a key enzyme in aerobic glycolysis)and NOD-like receptor thermal protein domain associated protein 3(NLRP3),and immunofluorescence assay was performed to observe the expression and distribution of PKM2.Results ① Our preliminary experiment identified that the optimal concentration of LPS for modeling was 20.0 μg/mL,a safe dosage range of PF was 0～100.0 μmol/L,and its optimal therapeutic concentration was 25.0 μmol/L.② Compared with the CON group,LPS stimulation resulted in significantly decreased cell viability(P<0.05),increased ECAR(P<0.05),elevated contents of IL-1β,IL-18,Lac and LDHA(P<0.05),up-regulated protein levels of p-PI3K,p-AKT,HIF-1α,p-PKM2 and NLRP3(P<0.05),and enhanced fluorescence intensity of PKM2 in the nucleus of cells(P<0.05).Compared with the model group,PF treatment reversed all above effects induced by LPS stimulation(all P<0.05).Compared with the LPS+PF group,in the LPS+PF+740Y-P group,ECAR was elevated(P<0.05),the contents of IL-1β,IL-18,Lac and LDHA were increased(P<0.05),and the relative expression levels of p-PI3K,p-AKT,HIF-1α,p-PKM2 and NLRP3 were increased(P<0.05),and the fluorescence intensity of PKM2 was strengthened(P<0.05)and enhanced in the nucleus(P<0.05).Conclusion PF reduces aerobic glycolysis in HK-2 cells and alleviates the inflammatory response by inhibiting the PI3K/AKT/HIF-1α signaling pathway.

Acute urinary retention(AUR)occurs frequently among astronauts on orbit.The current treatment is complex and easy to damage the urethra,which seriously affects the life and work of astronauts.In contrast,acupuncture,a traditional Chinese remedy,has shown promising results in managing urinary retention.However,the specific acupoints that could potentially prevent AUR remain uncertain due to the unique physiological conditions experienced by individuals in space compared to those on Earth.To address this gap,our research delved into the mechanisms of AUR and acupuncture within both traditional Chinese medicine and modern medical practices.We conducted a thorough literature review from Pubmed,Web of Science,CNKI,Wanfang database,VIP database and Chinese Medical Code database.A hierarchical evidence-scoring approach was utilized to analyze the included literatures,thus devised acupuncture protocols for the treatment of AUR.The outcomes of our study aim to establish a foundation for the application of acupuncture in managing AUR.

Under the influence of long-term space flights and the confined space environment,it is very easy to induce space depression syndrome,mainly manifested as decreased emotional stability,sleep disorders,mental fatigue,etc.,which seriously affect the living conditions and working abilities of astronauts.The current treatment methods mainly focus on psychological support and drug intervention.Acupuncture has a good effect in treating depression.Therefore,starting from the TCM pathogenesis and modern medical pathogenesis of aerospace depression syndrome,we conducted literature retrieval from databases such as the Chinese Medical Classic,China National Knowledge Infrastructure(CNKI),Wanfang,VIP,PubMed,and Web of science.For the included literature,we adopted the stratified evidence scoring method and combined the TCM mechanism and modern medical mechanism of the effect of acupuncture.A prescription for acupuncture points was constructed to provide a basis for selecting acupuncture points for the prevention of aerospace depression syndrome through acupuncture.

Objective To observe the effect of the GLP-1 receptor agonist liraglutide on β-cell function in patients newly diagnosed with type 2 diabetes patients.Methods Type 2 diabetes patients diagnosed between March 2020 and March 2021 in the Endocrinology Department of Yunnan Provincial Third People's Hospital were recruited and randomly divided into an experimental group and a control group.The experimental group was treated with liraglutide,a GLP-1 receptor agonist,for 6 months,while the control group received treatment with non-GLP-1 receptor agonists for 6 months(monotherapy or dual therapy).Changes in Weight,BMI,FPG,PG,HbA1c,FINS,FC-P,HOMA-IR,and HOMA-β levels were observed and measured before treatment and at 3 and 6 months after treatment.Results A total of 92 patients were included in the clinical observation(45 in the experimental group and 47 in the control group).Compared to baseline,both groups showed significant reductions in FPG,2hPG,and HbA1c at 3 and 6 months after treatment(P<0.01).FINS,HOMA-IR,and HOMA-β improved compared to pre-treatment levels(P<0.05).BMI decreased in the experimental group(P<0.05),while it slightly increased in the control group,but the difference was not statistically significant(P>0.05).Compared to the control group,the experimental group showed a greater reduction in FPG and 2hPG from baseline after 6 months of treatment,with statistically significant differences(P<0.05).HbA1c showed a certain decrease,but the difference was not statistically significant(P>0.05).FC-P in the experimental group was superior to pre-treatment levels at both 3 and 6 months(P<0.05),while in the control group,FC-P was only improved at the end of 6 months of treatment(P<0.05).Conclusion Early use of GLP-1 analogs in the treatment of newly diagnosed type 2 diabetes,as opposed to non-GLP-1 analog regimens,can lead to better restoration of β-cell function,weight reduction,and effective improvment of insulin resistance.

Objective To analyze the correlation between inflammatory factors and bone mineral density(BMD)as well as β-C-terminal telopeptide of type I collagen(β-CTX)in postmenopausal patients with type 2 diabetes mellitus(T2DM),and to evaluate the diagnostic efficacy of the inflammatory factors in postmenopausal T2DM patients with osteoporosis(OP).Methods A total of 538 postmenopausal women with T2DM,hospitalized in the Department of Endocrinology at the Third People's Hospital of Yunnan Province from October 1,2023 to August 31,2024,were screened,and 181 were ultimately included in the study.Based on bone mineral density,they were divided into the osteopenia group(86 patients,-2.51,B>0),while BMI was an independent protective factor for the occurrence of OP(OR<1,B<0);(4)ROC curve analysis showed that CRP,IL-6,NLR,MLR,and SII all demonstrated diagnostic efficacy for postmenopausal T2DM patients with osteoporosis,among which the combined detection model of CRP,IL-6,and SII exhibited the highest diagnostic efficacy.Conclusion Inflammatory markers are correlated with bone mineral density and β-CTX levels,and may have predictive value for diagnosing osteoporosis in postmenopausal T2DM patients.

OBJECTIVE To investigate the effect of myricetin(Myr) on immune function in rats with inflammatory bowel disease(IBD) by regulating the cAMP/PKA/CREB signaling pathway. METHODS IBD rat models were established and separated into control group, model group, low, medium, and high dose Myr(Myr-L, Myr-M, Myr-H, 28, 56, 112 mg·kg−1·d−1 Myr) groups, and high dose Myr+PKA inhibitor H89(Myr-H+H89 112 mg·kg−1·d−1 Myr+7 mg·kg−1·d−1 H89) group. The disease activity index(DAI) of rats was scored; immune function indicators and colon length were measured; the levels of IL-6, IL-17A, TNF-α, and cAMP in serum were determined by the kit; the pathological changes of colon tissue were observed by HE staining; the proportion of Treg cells was determined by flow cytometry; immunohistochemistry was used to detect the expression of MPO in colon tissue; Western blotting was used to determine cAMP/PKA/CREB signaling pathway related proteins. RESULTS Compared with the control group, the colon tissue cells in the model group were disorderly arranged, with a large number of inflammatory cell infiltration, severe ulceration, a large number of cell necrosis, mucosal edema, the DAI score, IL-6, TNF-α, and IL-17A levels, spleen coefficient, thymus coefficient, and MPO optical density values were obviously increased(P<0.05), the colon length, Treg cell ratio, cAMP concentration, p-PKA/PKA, and p-CREB/CREB levels were obviously reduced(P<0.05). Compared with the model group, the arrangement of colon tissue cells in the Myr-L, Myr-M, and Myr-H groups was relatively neat; mucosal edema inflammatory cell infiltration, cell necrosis and ulcer phenomenon were reduced; the DAI score, IL-6, TNF-α, and IL-17A levels, spleen coefficient, thymus coefficient, and MPO optical density values were gradually reduced(P<0.05); the colon length, Treg cell ratio, cAMP concentration, p-PKA/PKA, and p-CREB/CREB levels were gradually increased(P<0.05). Compared with the Myr-H group, the pathological changes in the colon tissue of the Myr-H+H89 group worsened, the DAI score, IL-6, TNF-α, and IL-17A levels, spleen coefficient, thymus coefficient, and MPO optical density values were obviously increased(P<0.05), the colon length, Treg cell ratio, cAMP concentration, p-PKA/PKA, and p-CREB/CREB levels were obviously reduced(P<0.05). CONCLUSION Myr may inhibit inflammation levels, regulate immune function, and exert protective effects on IBD rats by activating the cAMP/PKA/CREB signaling pathway.