ObjectiveTo observe the protective effect and mechanism of Tianhuang formula (THF) against renal injury in hyperuricemia nephropathy (HN) mice through network pharmacology. MethodAll mice were randomly divided into a normal group, a model group, a febuxostat group (5 mg·kg^-1), a low-dose THF group (L-THF, 60 mg·kg^-1), and a high-dose THF group (H-THF, 120 mg·kg^-1). The mice in the normal group were treated with 0.5% sodium carboxymethylcellulose (CMC-Na) by gavage daily. The HN model was induced by oral administration of 500 mg·kg^-1 hypoxanthine and intraperitoneal injection of 200 mg·kg^-1 oteracil potassium in mice except for those in the blank group. The mice in the groups with drug intervention were treated with corresponding drugs by gavage for three weeks. The levels of serum uric acid, creatinine, urea nitrogen, and 24-h albuminuria were measured. The renal injury was observed by hematoxylin-eosin (HE) staining and PAS staining, and renal fibrosis was observed by Sirius red staining. The effects and molecular mechanism of THF in HN mice were analyzed by Western blot, network pharmacology, and molecular docking. ResultBiochemical results indicated that compared with model group, BUN and 24 h urinary protein levels were significantly decreased in L-THF group (P<0.05), SUA and SCr levels were significantly decreased (P<0.01), and SUA, BUN, SCr and 24 h urinary protein levels in H-THF group were significantly decreased (P<0.01). The results of pathological staining showed that the kidney injury and interstitial fibrosis were improved in different doses of THF groups (P<0.05). Western blot results showed that the Nod-like receptor heat protein domain associated protein 3 (NLRP3) inflammatorome, interleukin-1β (IL-1β), fibronectin (FN), uric acid transporter 1 (URAT1), phosphorylated p65 (p-p65) and phosphorylated nuclear transcription factor (NF) -κB were inhibited in the H-THF group The expression of protein-producing α (p-IκBα) was reduced to the normal level (P<0.01), but the expression of IL-1β, URAT1 and p-IκBα in HN mice was not affected in the L-THF group. ConclusionTHF ameliorates renal inflammation and fibrosis by inhibiting the activation of NF-κB and NLRP3 inflammasomes to alleviate HN

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.

Osteosarcoma， a common primary bone malignancy， features high heterogeneity， poor prognosis， high propensity for local invasion and distant metastasis， and high mortality. At the moment， the major therapy is the combination of neoadjuvant chemotherapy and limb salvage surgery， which remarkably reduces the disability rate and fatality rate. However， long-term use of chemotherapeutic drugs leads to the acquisition of drug resistance by osteosarcoma cells and reduces the sensitivity of the tumor cells to the drugs. Thus， this therapy is not satisfactory. In recent years， amid the advancement in the treatment of tumor， Chinese medicine has attracted extensive attention for the obvious therapeutic effect and few adverse reactions. Phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） /mammalian target of rapamycin （mTOR） signaling pathway， as a classic cancer signaling pathway， is abnormally activated in osteosarcoma cells， which affects the proliferation， invasion， and metastasis of osteosarcoma cells by influencing the cycle of tumor cells， inhibiting apoptosis and autophagy of tumor cells， and promoting tumor angiogenesis. According to clinical research， Chinese medicine monomers influence proliferation， apoptosis， and autophagy of osteosarcoma cells and angiogenesis by regulating the activity of proteins in PI3K/Akt/mTOR signaling pathway， thereby suppressing osteosarcoma tissues and cells. Moreover， they can reverse the resistance of tumor cells to multiple anticancer drugs. Based on the knowledge and experience of Chinese medicine in the treatment of osteosarcoma， this paper reviews the role of PI3K/Akt/mTOR signaling pathway in the treatment of osteosarcoma by Chinese medicine monomers， which is expected to serve as a reference for the application of Chinese medicine in the treatment of osteosarcoma.

Objective    To explore the natural changes of procalcitonin (PCT) in the early period after pediatric cardiac surgery with cardiopulmonary bypass (CPB). Methods    A prospective and observational study was done on patients below 3 years of age, who underwent cardiac surgery involving CPB, with the risk adjustment of congenital heart surgery (RACHS) score of 2 to 5 and free from active preoperative infection or inflammatory disease. Blood samples for measurement of PCT, C-reactive protein (CRP) and white blood cell (WBC) were taken before surgery and daily for 7 days in postoperative period. Infections and complications within 7 days after operation were investigated. According to the presence or absence of infection and complications within 7 days after operation, the enrolled children were divided into an infection+complications group, a simple infection group, a simple complication group, and a normal group. Results     Finally, 429 children with PICU stay≥ 4 days were enrolled, including 268 males and 161 females, with a median age of 8.0 (0.7, 26.0) months. There were 145 children in the simple infection group, 38 children in the simple complication group, 230 children in the normal group and 16 children in the infection+complications group. The levels of PCT, CRP and WBC were significantly higher after CPB. CRP and WBC peaked on the second postoperative day (POD) and remained higher than normal until POD7. PCT peaked on POD1 and would generally decrease to normal on POD5 if without infection and complications. Age, body weight, RACHS scores, the duration of CPB and aortic cross-clamping time were correlated with PCT level. There was a statistical difference in PCT concentration between the simple infection group and the normal group on POD 3-7 (P<0.01) and a statistical difference between the simple complication group and the normal group on POD 1-7 (P<0.01). A statistical difference was found between the simple infection group and the simple complication group in PCT on POD 1-5 (P<0.05). Conclusion    WBC, CRP and PCT significantly increase after CPB in pediatric cardiac surgery patients. The factors influencing PCT concentration include age, weight, RACHS scores, CPB and aortic cross-clamping time, infection and complications.

ObjectiveTo study the association of serum adiponectin and high sensitivity C-reactive protein (hs-CRP) levels to short-term outcome in patients with acute ischemic stroke (AIS). MethodsClinical data of 216 patients with AIS in Beijing Bo'ai Hospital from January, 2019 to September, 2020 were collected. The serum biochemical indicator was measured in all the patients within 24 hours after enrollment, and adiponectin was detected with enzyme-linked immunosorbent assay. Meanwhile, all patients were evaluated with National Institute of Health Stroke Scale (NIHSS). Modified Rankin Scale (mRS) was used to assess the functional outcome 90 days after onset during follow-up. ResultsThe incidence of poor outcome in patients with AIS within 90 days was 48.1%. Compared with the good outcome group, the serum adiponectin was lower (t = 5.861, P < 0.001) and the serum hs-CRP level was higher (Z = 5.525, P < 0.001) poor outcome group. Reduced serum adiponectin (OR = 0.862, 95%CI 0.751 to 0.975, P < 0.001) and increased serum hs-CRP (OR = 1.215, 95%CI 1.015 to 1.455, P < 0.001) were independent risk factors for poor outcome in patients with AIS. The areas under curve (95% CI) of serum adiponectin and hs-CRP for predicting the outcome of patients with AIS were 0.819 (0.761 to 0.877) and 0.722 (0.654 to 0.791), respectively (P < 0.001). The predictive power of serum adiponectin was higher than that of hs-CRP (Z = 2.151, P = 0.032). The optimum cut-off point of adiponectin was < 3.5 mg/L, and the Yoden index was 0.609, yielding a sensitivity of 0.704 and a specificity of 0.905. ConclusionSerum adiponectin and hs-CRP can serve as independent predictors for short functional outcome in patients with AIS.

BACKGROUND: Chemotherapy is a common treatment for advanced hepatocellular carcinoma, but the effect is not satisfactory. The study aimed to retrospectively evaluate the effects of adding all-trans-retinoic acid (ATRA) to infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) for advanced hepatocellular carcinoma (HCC). METHODS: We extracted the data of patients with advanced HCC who underwent systemic chemotherapy using FOLFOX4 or ATRA plus FOLFOX4 at the Eastern Hepatobiliary Surgery Hospital, First Hospital of Jilin University, and Zhejiang Sian International Hospital and retrospectively compared for overall survival. The Cox proportional hazards model was used to calculate the hazard ratios for overall survival and disease progression after controlling for age, sex, and disease stage. RESULTS: From July 2013 to July 2018, 111 patients with HCC were included in this study. The median survival duration was 14.8 months in the ATRA plus FOLFOX4 group and 8.2 months in the FOLFOX4 only group ( P  < 0.001). The ATRA plus FOLFOX4 group had a significantly longer median time to progression compared with the FOLFOX4 group (3.6 months vs. 1.8 months, P  < 0.001). Hazard ratios for overall survival and disease progression were 0.465 (95% confidence interval: 0.298-0.726; P  = 0.001) and 0.474 (0.314-0.717; P  < 0.001) after adjusting for potential confounders, respectively. CONCLUSION ATRA plus FOLFOX4 significantly improves the overall survival and time to disease progression in patients with advanced HCC.
Humans ; Carcinoma, Hepatocellular/drug therapy* ; Retrospective Studies ; Liver Neoplasms/pathology* ; Oxaliplatin/therapeutic use* ; Fluorouracil/adverse effects* ; Disease Progression ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Leucovorin/adverse effects* ; Colorectal Neoplasms/drug therapy*

Osteosarcoma (OS) is the most common primary malignant bone tumor in clinic. It has high mortality and disability rate. Effective neoadjuvant chemotherapy combined with limb salvage surgery can improve the 5-year survival rate of OS patients. Drug resistance or low sensitivity of tumor cells is the most common cause of postoperative local recurrence and metastasis. Therefore, the sensitivity of OS cells to chemotherapy drugs is of great value to the prognosis of the patients. In recent years, traditional Chinese medicine has been widely used because of high efficiency and low toxicity. A large number of studies have confirmed that part of traditional Chinese medicine can reverse the chemotherapy resistance of OS cells by regulating the ABC transmembrane transport protein system. This article gives an overview of its related mechanisms and latest developments.

Objective To evaluate the efficacy of pulmonary surfactant(PS)in the treatment of acute respira﹣tory distress syndrome(ARDS)in the infants after congenital heart disease(CHD)operation. Methods The trial Was conducted from January 2012 to June 2017 in FuWai Hospital,and 90 infants Who had ARDS after cardiac surgery Were enrolled. They Were divided into 2 separate groups,PS group(conventional therapy +PS treatment,43 cases)and con﹣trol group(conventional therapy,47 cases). The clinical data,including age,body Weight,risk adjustment for congenital heart surgery 1(RACHS－1)degree,cardiopulmonary bypass( CPB)time,aortic occlusion time,mechanical ventila﹣tion time,intensive care unit(ICU)care time,mortality,complications,partial pressure of oxygen[pa(O2 )],fraction of inspiration O2(FiO2 )and pa(O2 )／FiO2(P／F),Were collected and analyzed. Results The average age,body Weight, RACHS－1 degree,CPB time and aortic occlusion time had no difference betWeen the 2 groups(P＞0. 05). After 24 h of treatment,pa(O2 )in PS group Was(94. 76 ± 13. 25)mmHg(1 mmHg﹦0. 133 kPa),Which Was significantly higher than that in control group[(67. 59 ± 7. 47)mmHg](P﹤0. 01). P／F in PS group Was 170. 37 ± 20. 62,Which Was sig﹣nificantly higher than that in control group(102. 65 ± 15. 29)( P﹤0. 01),While FiO2 in PS group Was(55. 18 ± 6. 89)%,Which Was significantly loWer than that in control group[(68. 59 ± 9. 59)%](P﹤0. 01). The mean me﹣chanical ventilation time[(194. 39 ± 26. 30)h]and ICU care time[(11. 64 ± 3. 26)d]of the experimental group Were shorter than control group[(288. 63 ± 26. 42)h and(16. 65 ± 4. 18)d],and the differences Were statistically significant(P﹤0. 01). Eight deaths occurred,PS group had 1 infant dead,and the control group had 7 deaths,so the mortality in PS group Was 2. 32%,loWer than that in control group(14. 89%),and the difference Was statistically sig﹣nificant(P﹤0. 01). Postoperative complications occurred in 23 patients,of Which PS group had 9 cases postoperative complications and control group had 15 cases,so the incidence of complications in PS group Was 20. 93%,loWer than that in control group(31. 91%),and the difference Was statistically significant(P ﹤0. 01). Conclusions PS has good efficacy in treating ARDS in infants With ARDS after congenital heart disease operation.

Objective     To recognize the risk factors of unplanned re-interventions within 30 days after pediatric cardiac surgery and evaluate the outcome of re-interventions. Methods     We retrospectively analyzed the clinical data of 202 children in Fuwai Hospital between January 1, 2015 and August 31, 2017. There were 115 males and 87 females at average age of 32.4 months with range of 3 days to 14 years. Results     There were 202 children who underwent unplanned re-intervention during 30 days post-operation, including 54 re-adjustments of pulmonary blood flow, 34 re-corrections for residual cardiac abnormalities, 28 cardiopulmonary resuscitations, 38 for coagulation problems, 19 pericardial drainages, 11 palliative re-operations to deliver heart load and 6 diaphragmatic folds and 12 others. The mortality rate among children who underwent unplanned re-inventions after cardiac surgery was 10.9% (22/202). It was much higher than those free from re-interventions (0.7%). Time of mechanical ventilation was 284.3 (11–2 339) h, and mean ICU stay was 17.7 (1–154) d, significantly longer than those free from re-interventions at the same period. Conclusion     Unplanned re-interventions after pediatric cardiac surgery is associated with higher mortality rate and longer recovery time. Early identifying risk factors and re-intervention can reduce the complications and improve the prognosis.

Objective To evaluate the efficacy of pulmonary surfactant (PS) on severe acute respiratory distress syndrome (ARDS) in different age baby with congenital heart disease. Methods We divided 43 baby patients into two separate groups including a little baby group (12 patients with age less than 3 months) and an infants group (31 patients with age of 3 months to one year). Both groups of patients were treated with intratracheal PS at the same time. The clinical data were collected and analyzed. Results The little baby group had lower body weight. There was no statistical difference in the cardiopulmonary bypass (CPB) time, operation blocking time, mechanical ventilation time, ICU stay time between the two groups (P>0.05). Before treatment, arterial partial presurre of oxygen (PaO2), fractional oxygen concentration in inspire gas (FiO2), the ratio of arterial PO2 to the inspired oxygen fraction (P/F) and arterial-alveolar N2 difference or gradient (a/A) had no difference between the two groups (P>0.05). After treatment, PaO2 and P/F of both groups were significantly lower than before (P<0.05), and FiO2 and P/F were significantly higher than before (P<0.05). After 24 h of treatment, PaO2 and P/F of the little baby group was significantly higher than that of the infants group (P<0.05), and FiO2 and P/F were significantly lower than those of the infants group (P<0.05). Conclusion PS treating severe ARDS in little baby with congenital heart disease has better effect than infants.