Objective:To evaluate the effect of the positive P-glycoprotein expression on the efficacy of patient-controlled intravenous analgesia (PCIA) with sufentanil or pentazocine in patients with cancer pain.Methods:This was a retrospective cohort study. The medical records of patients with cancer pain of either sex, aged 54-71 yr, weighing 49-67 kg, with TNM stage Ⅱ-Ⅳ, who were treated in People′s Hospital of Lishui from January 2020 to January 2024, were collected. The expression of P-glycoprotein in tumor tissues was determined by the immunohistochemical method. Patients with negative P-glycoprotein expression in tumor tissues were divided into 2 groups: sufentanil group (group S 1) and pentazocine group (group P 1). Patients with positive P-glycoprotein expression in tumor tissues were divided into 2 groups: sufentanil group (group S 2) and pentazocine group (group P 2). The patients in 4 groups received 48 h of PCIA when visual analogue scale > 5 cm. The PCIA solution contained sufentanil 2 &mu;g/kg and tropisetron 10 mg in 100 ml of normal saline in S 1 and S 2 groups or pentazocine 3 mg/kg+ tropisetron 10 mg in 100 ml of normal saline in P 1 and P 2 groups. The PCIA pump was set up to deliver a 1 ml bolus dose with a 10-min lockout interval and background infusion at 2 ml/h after a loading dose of 5 ml. Flurbiprofen 50 mg was intravenously injected when visual analogue scale > 3 cm during analgesia. The consumption of sufentanil, pentazocine and flurbiprofen within 4 h, >4-12 h, > 12-24 h and > 24-48 h of PCIA was recorded. The occurrence of adverse reactions such as respiratory depression (SpO 2<90%), nausea or/and vomiting, pruritus and bradycardia was recorded. Results:One hundred patients were finally included, with 25 in each group. There was no significant difference in the consumption of sufentanil, usage rate of flurbiprofen and incidence of respiratory depression, nausea and vomiting, pruritus and bradycardia during analgesia at each time period during PCIA between group S 1 and group S 2 ( P>0.05). Compared with group P 1, the consumption of pentazocinein was significantly increased within 4 h, > 4-12 h, and > 24-48 h of PCIA ( P<0.05), and no significant change was found in the usage rate of flurbiprofen at each time period and the incidence of respiratory depression, nausea or/and vomiting, pruritus and bradycardia during analgesia in group P 2 ( P>0.05). Conclusions:Positive P-glycoprotein expression may weaken the efficacy of PCIA with pentazocine, but exerts no effect on the efficacy of PCIA with sufentanil in patients with cancer pain.

Aim To express and purify recombinant hCGH-CTP fusion protein in high-density suspension culture of Chinese hamster ovary cells (CHO-S), and to verify the lipid accumulation effect of rhCGH-CTP on 3T3-L1 mature adipocytes. Methods The recombinant protein expression vector (pcDNA3. 1-rhCGH-CTP) was constructed, achieved by fusing the human glycoprotein hormone beta 5/alpha 2 cDNA with CTP Linker. The expression plasmid was transiently transfected into the suspended CHO-S to express rhCGH-CTP protein and then purified, and the protein biological activity was verified. Intervention with 3T3-L1 mature adipocyte cells for 24 h was performed to detect the changes of intracellular triglyceride (TG) level. Results Western blot results showed that rhCGH-CTP protein was successfully expressed in CHO-S cells, and the yield was up to 715. 4 mg • L~ . The secreted protein was purified by AKTA pure system with higher purity that was up to 90% as identified by SDS-PAGE. In addition, the intracellular cAMP content of mature adipocytes with high expression of TSHR gene significantly increased after intervention with different concentrations of rhCGH-CTP protein by ELISA kit, indicating that rhCGH-CTP protein had biological activity. Oil red 0 staining showed that compared with the control group, the lipid content of mature adipocytes in the intervention groups with different concentrations of rhCGH-CTP protein significantly decreased (P < 0. 05) . Conclusions The rhCGH-CTP protein has been successfully expressed and purified with biological activity, and effectively reduce TG. This research provides an important theoretical basis for further revealing the physiological role of CGH protein and its potential application in clinical practice.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.
Rats ; Animals ; Diabetic Nephropathies/drug therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Abelmoschus/chemistry* ; Podocytes ; Rats, Sprague-Dawley ; Epithelial-Mesenchymal Transition ; Flavones/pharmacology* ; Insulin Resistance ; Reactive Oxygen Species ; Diabetes Mellitus

Objective: To explore the safety and feasibility of stereotactic radiation therapy (SBRT) strategy for irradiating porcine ventricular septum, see if can provide a preliminary experimental evidence for clinical SBRT in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Five male pigs (39-49 kg, 6 months old) were used in this study. Pigs were irradiated at doses of 25 Gy (n=2) or 40 Gy (n=3). Delineation of the target volume was achieved under the guidance of 3-dimensional CT image reconstruction, and SBRT was then performed on defined target volume of porcine ventricular septum. Blood biomarkers, electrocardiogram and echocardiography parameters were monitored before and after SBRT. Pathological examination (HE staining, Masson staining) was performed on the target and non-target myocardium at 6 months post SBRT. Results: SBRT was successful and all animals survived to the designed study endpoint (6 months) after SBRT. Serum cardiac troponin T (cTnT) level was significantly higher than the baseline level at 1 day post SBRT, and reduced at 1 week after SBRT, but was still higher than the baseline level(P<0.05). Serum N-terminal pro-B type natriuretic peptide (NT-proBNP) was also significantly increased at 1 day post SBRT (P<0.05) and returned to baseline level at 1 week post SBRT. The serum NT-proBNP level was (249±78), (594±37) and (234±46) pg/ml, respectively, and the cTnT was (14±7), (240±40) and (46±34) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 40 Gy dose group. The serum NT-proBNP level was (184±20), (451±49) and (209±36) pg/ml, respectively, the cTnT values ​​were (9±1), (176±29) and (89±27) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 25 Gy dose group. Both NT-proBNP and cTnT values tended to be higher post SBRT in the 40 Gy dose group as compared with the 25 Gy dose group, but the difference was not statistically significant (P>0.05). The left ventricular ejection fraction and the left ventricular end-diastolic diameter remained unchanged before and after SBRT (P>0.05). The interventricular septum thickness showed a decreasing trend at 6 months after SBRT, but the difference was not statistically significant ((9.54±0.24) mm vs. (9.82±8.00) mm, P>0.05). The flow velocity of the left ventricular outflow tract, and the valve function and morphology were not affected by SBRT. At 6 months after SBRT, HE staining revealed necrosis in the irradiated target area of ​​the myocardium in the 40 Gy dose group and the 25 Gy dose group, and the degree of necrosis in the irradiated interventricular septum was more obvious in the 40 Gy dose group as compared with the 25 Gy group. The combined histological analysis of the two groups showed that the necrotic area of ​​the irradiated target area accounted for (26±9)% of the entire interventricular septum area, which was higher than that of the non-irradiated area (0) (P<0.05). There was no damage or necrosis of myocardial tissue outside the target irradiation area in both groups. The results of Masson staining showed that the percentage area of myocardial fibrosis was significantly higher in the irradiated target area than non-irradiated area ((12.6±5.3)% vs. (2.5±0.8)%, P<0.05). Conclusion: SBRT is safe and feasible for irradiating porcine ventricular septum.
Animals ; Feasibility Studies ; Male ; Necrosis ; Radiosurgery/methods* ; Stroke Volume ; Swine ; Ventricular Function, Left ; Ventricular Septum

International guidelines regarding the role of intravenous immunoglobulin (IVIG) in the management of Rh- and ABO-mediated haemolytic disease of the newborn was drafted by an international panel of experts in the fields of hematology, neonatology, and blood transfusion and was published in British Journal of Haematology on March 16, 2022. The guidelines summarize the evidence-based practice of IVIG in Rh- and ABO-mediated haemolytic disease of the newborn and propose related recommendations. The guidelines recommend that IVIG should not be applied as a routine treatment regimen for Rh- and ABO-mediated haemolytic disease of the newborn in order to reduce exchange transfusion (ET), and the best time to apply IVIG remains unclear in the situations where hyperbilirubinaemia is severe (approaching or exceeding the ET threshold) or ET cannot be implemented. These guidelines are formulated with rigorous methods, but with the lower quality of evidence.
Infant, Newborn ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Erythroblastosis, Fetal/drug therapy* ; Exchange Transfusion, Whole Blood ; Hematologic Diseases ; Hyperbilirubinemia

The antidepressant effect of Xiaoyaosan has been demonstrated. It is of value to explore the biological mechanism of Xiaoyaosan in the treatment of depression from the perspective of functional modules by using the method of functional module division of the metabolic network. The differential metabolites and related enzymes and proteins regulated by Xiaoyaosan were identified in the database. Pathway enrichment analysis and crosstalk pathway analysis of Xiaoyaosan regulated metabolites was carried out. A network of differentially regulated metabolites and their enzymes and proteins was constructed by using the STRING tool. The CNM decomposition algorithm was used to extract the functional modules of the network and enrichment analysis of functional modules was carried out. The results show that Xiaoyaosan regulates 97 differential metabolites, 234 related enzymes and 258 depression-related proteins. The pathways crosstalk analysis was divided into two sub-networks, one of which is related to the neural system and cell signal transduction, the other is related to the endocrine system and metabolic pathways. KEGG pathway enrichment analysis of the network and 9 functional modules extracted by the CNM algorithm shows that module 1 and module 3 belong to the pathways that can be enriched into more pathways with fewer proteins. The corresponding functions of these pathways include the endocrine system, amino acid metabolism, the nervous system and signal transduction. In this study, pathway crosstalk analysis and metabolic network module division strategies were used to explain the biological mechanism of Xiaoyaosan in the treatment of depression, providing ideas and methods for in-depth study of the pharmacological mechanism of this traditional Chinese medicine from the perspective of metabolic regulation.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Objective::To observe the intervention effect of Yiqi Huoxue recipe (YQHX) on ventricular remodeling in rats with chronic heart failure, in order to explore its mechanism. Method::Among 40 male SD rats, 10 were randomly selected as the sham operation group. The left anterior descending coronary artery ligation was performed to construct the chronic heart failure(CHF) rat model. After modeling, they were randomly divided into model group, captopril group(13.5 mg·kg^-1·d^-1) and YQHX group (20 g·kg^-1·d^-1), and orally given the corresponding drugs. After 8 weeks of intervention, cardiac tissues were collected, body mass and heart mass were weighed, and echocardiography were performed to detect the changes in cardiac structure. Masson staining was performed to determine the myocardial interstitial collagen volume fraction. Western blot was used to detect the expression levels of mitochondrial fusion protein optic atrophy 1 (Opa1) and cleavage protein dynamic-related protein 1 (Drpl). The quantitative real-time fluorescence polymerase chain reaction(Real-time PCR)was applied to detect the expressions of Wnt/β-catenin pathway-related factors such as lipoprotein receptor-related protein 6 (LRP6), glycogen synthase kinase-3β (GSK-3β) and β-catenin. Result::Compared with the sham group, the left ventricular wall of the model group was significantly thickened (P<0.05), the cardiac cavity was significantly enlarged, and the content of collagen in the myocardial interstitium was increased (P<0.01). The expression level of Opal decreased, the expression level of Drp1 increased (P<0.05), the mRNA expression level of LRP6, GSK-3, and β-catenin increased (P<0.01). Compared with the model group, YQHX group can reduce ventricular wall thickening, heart chamber enlargement, myocardial interstitial collagen content, up-regulate the low expression of Opa1, but down-regulate the high expressions of Drpl, LRP6, GSK-3β, β-catenin(P<0.05, P<0.01). Conclusion::YQHX can effectively alleviate ventricular remodeling and improve mitochondrial energy metabolism in rats with CHF. The mechanism may be related to the inhibition of Wnt/β-catenin related factors.