Obesity， a global chronic disease， is associated with adipose tissue dysfunction， which is one of the contributing factors to obesity. The cyclic adenosine monophosphate （cAMP） signaling pathway， a key regulator of lipid metabolism， plays a pivotal role in obesity development. Various of traditional Chinese medicine monomers， such as flavonoids， lignans， phenols， and terpenoids， as well as traditional Chinese medicine compound formulas like Xiaoyao powder， Shengmai powder， and Zexie decoction， can maintain energy homeostasis， balance adipose tissue function， regulate glucose metabolism， improve insulin resistance， and suppress inflammatory responses through cAMP signaling pathway regulation， thereby intervening in lipid metabolism for obesity treatment. Although a substantial amount of basic research has preliminarily elucidated the potential mechanisms by which traditional Chinese medicine intervenes in obesity through the cAMP signaling pathway， clinical translational research remains inadequate. There is an urgent need for large-sample， high-quality randomized controlled trials to validate these findings.

ObjectiveTo investigate the effect of solute carrier family 7 member 5 (SLC7A5) inhibitor JPH203 on renal fibrosis induced by unilateral ureteral obstruction in mice. MethodsSixteen SPF male C57BL/6 mice were randomly divided into the control group and the experimental group, with 8 mice in each group. The mouse model of renal fibrosis was established by unilateral ureteral obstruction. From the third day after surgery, the mice in the control group were intraperitoneally injected with phosphate-buffered saline (PBS) for 11 consecutive days, and the injection dose was 200 μL/d. Mice in the experimental group received intraperitoneal injection of JPH203 (50 mg/kg) every day for 11 days. On day 14, the mice were euthanized, then the kidney tissues were obtained. Hematoxylin and eosin (HE) staining was used to assess renal tissue damage, Masson staining was used to evaluate collagen fiber deposition in the extracellular matrix, and immunohistochemistry was used to detect the levels of fibroblast activation markers α-smooth muscle actin (α-SMA) and collagen type Ⅰ (COL-Ⅰ) in kidney tissues. Western blotting was further performed to measure the expression levels of SLC7A5 and transforming growth factor-β1 (TGF-β1), as well as the phosphorylation levels of mammalian target of rapamycin complex 1 (mTORC1) signaling pathway-related molecules. Real-time quantitative PCR was used to verify changes in the mRNA levels of SLC7A5, α-SMA, and COL-Ⅰ in kidney tissues. ResultsCompared with the control group, the experimental group showed reduced destruction of renal tissue structure and a significantly lower pathological injury score (P<0.05). Additionally, collagen deposition in the extracellular matrix was decreased, and the percentage of collagen fiber area was significantly reduced (P<0.001) in the experimental group. The levels of fibroblast activation markers α-SMA and COL-Ⅰ were significantly lower in the experimental group (both P<0.001). The expression levels of SLC7A5 and TGF-β1 were also significantly decreased (P<0.001), and the phosphorylation levels of mTORC1 signaling pathway-related proteins 4E-BP1 and mTORC1 were significantly reduced (P<0.001). Real-time quantitative PCR confirmed that the mRNA levels of SLC7A5, α- SMA, and COL-Ⅰ in kidney tissues were significantly lower in the experimental group (P<0.001). ConclusionJPH203 may inhibit the progression of renal fibrosis in mice by suppressing SLC7A5 expression, regulating the mTORC1 signaling pathway, and altering fibroblast activation status.

Huanglian Jiedutang （HLJDT）， as a classical formula for clearing heat and removing toxins， has been widely applied in the treatment of various clinical diseases in recent years， particularly during the fire-heat stage of stroke， where it has attracted considerable attention. Based on previous studies， this paper systematically elaborates on the research progress on the active components of HLJDT， its clinical application in ischemic stroke， and advances in studies on its mechanisms of action. Modern pharmacological studies have demonstrated that HLJDT contains multiple active components， including baicalin， geniposide， and berberine. In the treatment of ischemic stroke， these components exert therapeutic effects through multi-target， multi-pathway， and multi-level mechanisms. Clinical studies have shown that HLJDT can increase cerebral blood flow， reduce cerebral infarct volume， and improve post-stroke physical dysfunction in patients with ischemic stroke. Experimental studies have indicated that HLJDT can improve neurological function scores and increase cerebral perfusion in experimental stroke models. In addition， the mechanisms underlying the anti-ischemic stroke effects of HLJDT may be related to anti-inflammatory and antioxidant activities， promotion of angiogenesis， and regulation of amino acid and energy metabolism. Although existing studies have confirmed that HLJDT exhibits multi-target and multi-pathway synergistic therapeutic characteristics， further large-sample randomized controlled trials are still needed to verify its long-term efficacy and to further elucidate the dynamic interaction network among components， targets， and pathways. Combined with network pharmacology and molecular docking analyses， this study further clarifies the synergistic targets of the core components （berberine， baicalin， and geniposide）， providing a theoretical basis for in-depth research and clinical translation of HLJDT in the treatment of ischemic stroke.

Objective To investigate the impact of variations in volute cross-sectional area on the flow characteristics and hemolytic performance of centrifugal blood pumps by designing six volute structures.Methods Computational fluid dynamics and the Lagrangian method were used to analyze flow characteristics and predict hemolysis in blood pumps with different volute designs.Results The annular volute pump showed the poorest hydraulic performance,while the hydraulic performance of the S-shaped volute was the best,which was improved by 35.29％compared to that of the annular volute.Some volutes experienced stagnation zones at the helical inlet(0°-90°)and significant backflow at the outlet(270°-360°).The downward concave-shaped volute had the highest hemolysis index(HI),i.e.,9.59×10-4.Meanwhile,the HI of the annular volute was the lowest,which was 71.85％less than the concave-shaped volute.Conclusions Reducing the gradient of the area variation at the helical inlet and outlet can prevent flow stagnation and backflow.A higher HI arises due to the prolonged exposure of red blood cells to high shear stress.This study provides a theoretical basis for designing and optimizing volute structures of centrifugal blood pumps.

Objective To study the effects of different clearance conditions(equal upper and lower axial clearance,change of upper/lower axial clearance,axial displacement of blades)on efficiency and hemolysis performance of blood pump.Methods The blood pumps under three kinds of clearance conditions were numerically simulated by computational fluid dynamics.Results For efficiency,when the upper and lower axial clearance was equal,the lower axial clearance was unchanged and the upper axial clearance was reduced,the efficiency of blood pump could be improved by 0.85%,1.71%and 2.90%,respectively.While the upper shaft clearance remained unchanged,the lower shaft clearance was decreased by 1.18%.For hemolysis,the increase of the clearance could reduce the hemolysis index(HI)under the first two clearance conditions,while the axial migration of the blade wheel would increase the HI.When the upper axial clearance was unchanged and the lower axial clearance was 0.3 mm,the HI was the largest,which was 8.65×10-4.When the upper and lower axial clearance was 0.7 mm,the HI was the smallest,which was 4.51×10-4.Conclusions Improving blood pump clearance is helpful to optimize the performance of blood pump.This study can provide some references for the design and optimization of interstitial structure of blood pump.

Objective To investigate the impact of variations in volute cross-sectional area on the flow characteristics and hemolytic performance of centrifugal blood pumps by designing six volute structures.Methods Computational fluid dynamics and the Lagrangian method were used to analyze flow characteristics and predict hemolysis in blood pumps with different volute designs.Results The annular volute pump showed the poorest hydraulic performance,while the hydraulic performance of the S-shaped volute was the best,which was improved by 35.29％compared to that of the annular volute.Some volutes experienced stagnation zones at the helical inlet(0°-90°)and significant backflow at the outlet(270°-360°).The downward concave-shaped volute had the highest hemolysis index(HI),i.e.,9.59×10-4.Meanwhile,the HI of the annular volute was the lowest,which was 71.85％less than the concave-shaped volute.Conclusions Reducing the gradient of the area variation at the helical inlet and outlet can prevent flow stagnation and backflow.A higher HI arises due to the prolonged exposure of red blood cells to high shear stress.This study provides a theoretical basis for designing and optimizing volute structures of centrifugal blood pumps.

Objective:To explore the risk factors of deaths caused by influenza-associated encephalopathy (IAE) in children.Methods:A case control study was conducted.The clinical data (including baseline fata, organ function indices, inflammatory factors, imaging data, treatment, and outcomes) of IAE children hospitalized in the pediatric intensive care unit (PICU) of Shanghai Children′s Hospital, School of Medicine, Shanghai Jiao Tong University from January 2020 to December 2023 were retrospectively analyzed.The children were divided into a survival group and a death group.The Logistic regression and receiver operating characteristic (ROC) curve were used to analyze the risk factors of death in IAE children.Results:A total of 46 cases were included, with an onset age of 74.8(46.0, 92.5) months.The main cause of IAE was influenza A virus infection, which was detected in 45 cases(97.8%), and 32 cases (69.6%) of them had H3N2.One child (2.2%) was infected by influenza B virus.Eight children died, showing a mortality of 17.4%.There was significant difference in Glasgow Coma Scale between the survival and death groups when they were admitted into the PICU [10 (9, 11) points vs.3 (3, 5) points] ( Z=-4.510, P<0.05).All patients in the death group had multiple organ dysfunction syndrome, respiratory failure and circulatory system failure.Serum procalcitonin (PCT)[15.7 (3.3, 37.4) μg/L], interleukin-6 (IL-6)[1 039.1 (319.3, 2 884.3) ng/L], and cerebrospinal fluid protein(CSFP)[13 050.0 (5 865.0, 21 100.0) mg/L] in the death group compared with those in the survival group [0.2 (0.1, 0.8) μg/L, 15.5 (7.9, 44.8) ng/L, 227.0 (190.0, 332.0) mg/L]were highly increased ( Z=-3.364, -4.088, -3.757, all P<0.001).Logistic regression analysis showed that PCT ( OR=0.660, P<0.05), IL-6 ( OR=1.014, P<0.05) and CSFP ( OR=1.001, P<0.05) were risk factors of death in IAE.The areas under the ROC curve for these three factors were 0.88 (95% CI: 0.77-0.97), 0.96 (95% CI: 0.86-1.00) and 0.93 (95% CI: 0.76-1.00), respectively.When a cutoff value of 2.50 μg/L, 269.67 ng/L and 5 240.00 mg/L was taken, PCT achieved a sensitivity of 0.875 and a specificity of 0.816, IL-6 achieved a sensitivity of 0.875 and specificity of 0.974, and CSFP achieved a sensitivity of 0.875 and specificity of 0.974, respectively. Conclusions:High levels of serum PCT, IL-6 and CSFP at PICU admission are risk factors of poor prognosis in children with IAE.

Objective:To explore the clinical features and risk factors for pediatric severe Mycoplasma pneumoniae pneumonia (SMPP) complicated with pulmonary embolism. Methods:SMPP patients admitted to Department of Pediatrics, Jiaxing First Hospital and Pediatric Intensive Care Unit, Shanghai Children′s Hospital from December 2019 to December 2023 were included in this retrospective case-control study.According to whether they were complicated with pulmonary embolism, SMPP patients were divided into a pulmonary embolism group and a non-pulmonary embolism group.Clinical characteristics of the two groups, including general data, laboratory examination and imaging data were compared and analyzed.The t-test and Mann-Whitney rank-sum test were used to compare the measurement data, and the χ2 test was used to compare the count data.The risk factors of SMPP patients developing pulmonary embolism were analyzed by the univariate method. Results:There were 10 out of 62 SMPP children developing pulmonary embolism, showing an incidence of 16.13%.In the pulmonary embolism group, there were 5 boys and 5 girls, with a median age of 7.50 (5.75, 9.25) years.There were 52 children in the non-pulmonary embolism group, including 29 boys and 23 girls, with a median age of 6.50(5.00, 8.00)years.The hospitalization time, body temperature, total white blood cell count, neutrophil count, C-reactive protein levels, lactate dehydrogenase levels, prothrombin time, activated partial thromboplastin time, D-dimer (D-D) levels, fibrinogen degradation product levels, pleural effusion and atelectasis rates in the pulmonary embolism group were significantly higher than those in the non-pulmonary embolism group (all P<0.05). Fibrinogen levels in the pulmonary embolism group were significantly lower than those in the non-pulmonary embolism group ( P<0.05). Univariate Logistic regression analysis showed that the D-D level was a risk factor for SMPP patient developing pulmonary embolism.The receiver operating characteristic curve analysis revealed that the D-D level had the largest area under the curve for predicting pulmonary embolism of 0.990(95% CI: 0.972-1.000, P<0.001), with a sensitivity of 100%, a specificity of 92%, and a cut-off value of 4.63 mg/L. Conclusions:SMPP children complicated with pulmonary embolism are prone to high inflammation and impaired coagulation function.The increase of D-D levels is a risk factor for the development of pulmonary embolism in SMPP.

Objective:To explore the risk factors of deaths caused by influenza-associated encephalopathy (IAE) in children.Methods:A case control study was conducted.The clinical data (including baseline fata, organ function indices, inflammatory factors, imaging data, treatment, and outcomes) of IAE children hospitalized in the pediatric intensive care unit (PICU) of Shanghai Children′s Hospital, School of Medicine, Shanghai Jiao Tong University from January 2020 to December 2023 were retrospectively analyzed.The children were divided into a survival group and a death group.The Logistic regression and receiver operating characteristic (ROC) curve were used to analyze the risk factors of death in IAE children.Results:A total of 46 cases were included, with an onset age of 74.8(46.0, 92.5) months.The main cause of IAE was influenza A virus infection, which was detected in 45 cases(97.8%), and 32 cases (69.6%) of them had H3N2.One child (2.2%) was infected by influenza B virus.Eight children died, showing a mortality of 17.4%.There was significant difference in Glasgow Coma Scale between the survival and death groups when they were admitted into the PICU [10 (9, 11) points vs.3 (3, 5) points] ( Z=-4.510, P<0.05).All patients in the death group had multiple organ dysfunction syndrome, respiratory failure and circulatory system failure.Serum procalcitonin (PCT)[15.7 (3.3, 37.4) μg/L], interleukin-6 (IL-6)[1 039.1 (319.3, 2 884.3) ng/L], and cerebrospinal fluid protein(CSFP)[13 050.0 (5 865.0, 21 100.0) mg/L] in the death group compared with those in the survival group [0.2 (0.1, 0.8) μg/L, 15.5 (7.9, 44.8) ng/L, 227.0 (190.0, 332.0) mg/L]were highly increased ( Z=-3.364, -4.088, -3.757, all P<0.001).Logistic regression analysis showed that PCT ( OR=0.660, P<0.05), IL-6 ( OR=1.014, P<0.05) and CSFP ( OR=1.001, P<0.05) were risk factors of death in IAE.The areas under the ROC curve for these three factors were 0.88 (95% CI: 0.77-0.97), 0.96 (95% CI: 0.86-1.00) and 0.93 (95% CI: 0.76-1.00), respectively.When a cutoff value of 2.50 μg/L, 269.67 ng/L and 5 240.00 mg/L was taken, PCT achieved a sensitivity of 0.875 and a specificity of 0.816, IL-6 achieved a sensitivity of 0.875 and specificity of 0.974, and CSFP achieved a sensitivity of 0.875 and specificity of 0.974, respectively. Conclusions:High levels of serum PCT, IL-6 and CSFP at PICU admission are risk factors of poor prognosis in children with IAE.

Objective:To explore the clinical features and risk factors for pediatric severe Mycoplasma pneumoniae pneumonia (SMPP) complicated with pulmonary embolism. Methods:SMPP patients admitted to Department of Pediatrics, Jiaxing First Hospital and Pediatric Intensive Care Unit, Shanghai Children′s Hospital from December 2019 to December 2023 were included in this retrospective case-control study.According to whether they were complicated with pulmonary embolism, SMPP patients were divided into a pulmonary embolism group and a non-pulmonary embolism group.Clinical characteristics of the two groups, including general data, laboratory examination and imaging data were compared and analyzed.The t-test and Mann-Whitney rank-sum test were used to compare the measurement data, and the χ2 test was used to compare the count data.The risk factors of SMPP patients developing pulmonary embolism were analyzed by the univariate method. Results:There were 10 out of 62 SMPP children developing pulmonary embolism, showing an incidence of 16.13%.In the pulmonary embolism group, there were 5 boys and 5 girls, with a median age of 7.50 (5.75, 9.25) years.There were 52 children in the non-pulmonary embolism group, including 29 boys and 23 girls, with a median age of 6.50(5.00, 8.00)years.The hospitalization time, body temperature, total white blood cell count, neutrophil count, C-reactive protein levels, lactate dehydrogenase levels, prothrombin time, activated partial thromboplastin time, D-dimer (D-D) levels, fibrinogen degradation product levels, pleural effusion and atelectasis rates in the pulmonary embolism group were significantly higher than those in the non-pulmonary embolism group (all P<0.05). Fibrinogen levels in the pulmonary embolism group were significantly lower than those in the non-pulmonary embolism group ( P<0.05). Univariate Logistic regression analysis showed that the D-D level was a risk factor for SMPP patient developing pulmonary embolism.The receiver operating characteristic curve analysis revealed that the D-D level had the largest area under the curve for predicting pulmonary embolism of 0.990(95% CI: 0.972-1.000, P<0.001), with a sensitivity of 100%, a specificity of 92%, and a cut-off value of 4.63 mg/L. Conclusions:SMPP children complicated with pulmonary embolism are prone to high inflammation and impaired coagulation function.The increase of D-D levels is a risk factor for the development of pulmonary embolism in SMPP.