Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Objective:To explore the mechanism of early pancreatic exocrine function changes in severely scalded rats.Methods:The experimental research methods was used. Eighty male Sprague-Dawley rats aged 7-8 weeks were divided into simple sham injury group ( n=8), sham injury+cholecystokinin octapeptide (CCK8) group ( n=8), severe scald+CCK8 group ( n=32), and extremely severe scald+CCK8 group ( n=32) by the random number table, which were treated accordingly. Immediately after injury of rats in the 2 sham injury groups and 1, 2, 3, and 7 days after injury of rats in the 2 scald groups, the improved methods including pancreatic duct puncture and catheterization were used to dynamically collect the pancreatic-bile juice (PBJ) of rats. The PBJ secretory volume within 1 h was recorded, and the content of pancreatic lipase, α-amylase, and trypsin in PBJ was detected by enzyme-linked immunosorbent assay (ELISA), and the number of samples was 8. The femoral venous blood was collected, and the concentrations of pancreatic lipase and α-amylase in serum were detected by standard colorimetry to reflect their activity ( n=8). The pancreatic tissue was extracted, and the levels of interleukin-1β (IL-1β) and IL-6 in pancreatic tissue were detected by ELISA ( n=8), the expression of hypoxia-inducible factor 1α (HIF-1α) in pancreatic tissue was detected by immunofluorescence method, and the histopathological changes in pancreatic tissue were observed by hematoxylin-eosin staining, the severity of pancreatic tissue injury in the 2 scald groups was evaluated by modified Schmidt method ( n=6), and the ultrastructure of acinar cells in pancreatic tissue was observed by transmission electron microscopy. Data were statistically analyzed with analysis of variance for factorial design, Tukey test, independent sample t test, and least significant difference test. Results:Compared with the PBJ secretory volume (0.740±0.030) mL in the pancreatic tissue of rats in simple sham injury group within 1 h immediately after injury, the (0.823±0.033) mL in sham injury+CCK8 group was significantly increased ( t=4.92, P<0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the PBJ secretory volume of rats within 1 h in severe scald+CCK8 group ((0.681±0.024), (0.608±0.056), (0.525±0.025), and (0.720±0.044) mL) and extremely severe scald+CCK8 group ((0.540±0.025), (0.406±0.021), (0.475±0.036), and (0.690±0.018) mL) was significantly decreased on 1, 2, 3, and 7 days after injury ( P<0.05). Compared with that in severe scald+CCK8 group, the PBJ secretory volume of rats within 1 h in extremely severe scald+CCK8 group was significantly decreased on 1 and 2 days after injury ( P<0.05). Compared with that of rats in simple sham injury group immediately after injury, the content of pancreatic lipase, α-amylase, and trypsin in PBJ of rats in sham injury+CCK8 group immediately after injury was significantly increased (with t values of 4.56, 3.30, and 4.99, respectively, P<0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the content of pancreatic lipase and α-amylase in PBJ of rats in severe scald+CCK8 group and extremely severe scald+CCK8 group was significantly decreased on 1, 2, 3, and 7 days after injury ( P<0.05), the trypsin content in PBJ of rats in extremely severe scald+CCK8 group was significantly decreased on 2 days after injury ( P<0.05). Compared with that in severe scald+CCK8 group, the content of pancreatic lipase in PBJ of rats in extremely severe scald+CCK8 group was significantly decreased on 1, 2, and 3 days after injury ( P<0.05), and the content of α-amylase and trypsin in PBJ was significantly decreased on 1 and 2 days after injury ( P<0.05). There were no statistically significant differences in the activities of pancreatic lipase and α-amylase in serum of rats among the 4 groups at various time points after injury ( P>0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the levels of IL-1β in pancreatic tissue of rats in severe scald+CCK8 group on 1, 2, and 3 days after injury and in extremely severe scald+CCK8 group on 1, 2, 3, and 7 days after injury were significantly increased ( P<0.05), and the levels of IL-6 in pancreatic tissue of rats in severe scald+CCK8 group and extremely severe scald+CCK8 group were significantly increased on 1, 2, 3, and 7 days after injury ( P<0.05). Compared with that in severe scald+CCK8 group, the IL-1β level in pancreatic tissue of rats in extremely severe scald+CCK8 group was significantly increased on 2 and 3 days after injury ( P<0.05), and IL-6 level in pancreatic tissue was significantly increased on 2 days after injury ( P<0.05). The expression levels of HIF-1α in pancreatic tissue of rats in simple sham injury group and sham injury+CCK8 group immediately after injury were lower; and compared with that in sham injury+CCK8 group immediately after injury, the expression levels of HIF-1α in pancreatic tissue of rats in the 2 scald groups increased to a certain extent at different time points after injury, and the expression position was transited from the edge of the pancreatic tissue to the whole pancreas, the expression levels of HIF-1α in pancreatic tissue of rats in the 2 scald groups tended to be normal on 7 days after injury. Compared with that in simple sham injury group immediately after injury, the proportion of acinar cell cytoplasm in pancreatic tissue of rats in sham injury+CCK8 group was increased; and with the increase of time after injury, edema, hemorrhage, necrosis, and inflammatory infiltration appeared in pancreatic tissue of rats in the 2 scald groups. Compared with that in severe scald+CCK8 group, the scores of edema, inflammatory cell infiltration, bleeding, and necrosis in pancreatic tissue of rats in extremely severe scald+CCK8 group were increased to varying degrees at various time points after injury, and the scores of pancreatic tissue of rats in the 2 scald groups basically recovered to normal on 7 days after injury. Compared with that in simple sham injury group immediately after injury, the number of enzyme granules in acinar cells of pancreatic tissue of rats in sham injury+CCK8 group was increased, and with the increase of time after injury, the enzyme granules in acinar cells of rats in the 2 scald groups were gradually reduced basically. Conclusions:The exocrine functions of pancreas, such as synthesis and secretion of pancreatic enzymes, are decreased in the early stage in severely scalded rats. And the greater the scalded area, the more significant the decline of pancreatic exocrine function. This change may be related to hypoxic injury and inflammation in pancreatic tissue after severe scald.

Background Environmental pollutants can affect N⁶-methyladenosine (m⁶A) level in the body, but the change of m⁶A level in kidney after being exposed to cadmium (Cd) and the molecular mechanism of renal injury need to be further studied. Objective To analyze the associations of m⁶A modification and methyltransferases/demethylases with microRNA-21 (miR-21) and transforming growth factor- β1 (TGF - β1) in kidney of rats exposed to Cd. Methods Twenty-four SPF male SD rats were divided into 4 groups, with 6 rats in each group, and were exposed to Cd by subcutaneous injection of 2.0, 1.0, and 0.5 mg·kg⁻¹ cadmium chloride (CdCl₂) and equal volume of normal saline for 2 weeks, 7 d a week, respectively. The levels of N-acetyl-β-D-glucosidase (UNAG) and albumin (UALB) in urine, and the levels of m⁶A methylation and TGF-β1 in kidney were detected by enzyme-linked immunosorbent assay (ELISA). The level of blood urea nitrogen (BUN) was measured by urease method. The levels of renal oxidative stress indicators such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were detected by total bile acid method, water-soluble tetrazolium asssay, and colorimetric method respectively. The relative levels of TGF-β1, methyltransferases, and demethylases in kidney were measured by reverse transcription-polymerase chain reaction. The expression of miR-21 in kidney was detected by fluorescent quantitative polymerase chain reaction. Results After 2 weeks of exposure to Cd, the body weights of rats in the 2.0 and 1.0 mg·kg⁻¹ cadmium chloride groups decreased, and the ratio of kidney/body weight and the levels of BUN, UNAG, and TGF-β1 mRNA and protein increased in the 2.0 mg·kg⁻¹ cadmium chloride group (P<0.05). The expression levels of m⁶A modification, methyltransferases METTL3, METTL14, Wilms’ tumor 1-associated protein (WTAP), and miR-21 were increased both in the 2.0 and 1.0 mg·kg⁻¹ cadmium chloride groups, with significant differences compared with the control group (P<0.05). The results of correlation analysis showed that the m⁶A modification level was negatively correlated with SOD (r=−0.4489, P<0.05) and GSH-Px (r=−0.4874, P<0.05), METTL3 was negatively correlated with MDA (r=−0.5158, P<0.05), while there was a positive correlation between FTO and GSH-Px (r=0.4802, P<0.05). In addition, miR-21 was positively correlated with METTL3 (r=0.7491), METTL14 (r=0.6157), and WTAP (r=0.6660) (P<0.05), TGF-β1 was positively correlated with METTL3 (r=0.5025, P<0.05) but negatively correlated with FTO (r=−0.5634, P<0.05) . Conclusion Cd can induce m⁶A methylation and up-regulation of METTL3, METTL14, WTAP, and miR-21 expression levels in rat kidney tissues, indicating that m⁶A and miR-21 may be associated with Cd-induced renal fibrosis.

Objective:To compare the short-term clinical outcomes of patients undergoing laparoscopic versus open radical resection of hilar cholangiocarcinoma.Methods:The clinical data of 91 patients who underwent radical resection for hilar cholangiocarcinoma at our hospital from January 2018 to June 2021 were analyzed retrospectively. There were 48 males and 43 females, with aged of (61.51±7.18) years old. The patients were divided into the laparotomy group ( n=59) and the laparoscopic group ( n=32) based on the operations they received. The general data, perioperative data and complications of the two groups were compared. Results:There was no perioperative death in the laparoscopic group, but one patient died of abdominal bleeding in the laparotomy group. All other patients recovered from postoperative complications with treatment. When compared with patients in the laparotomy group, the operation time [(381.28±102.37) vs. (296.81±84.74) min] and biliary intestinal anastomosis time [(17.81±2.81) vs. (15.19±2.27) min] were significantly longer in the laparoscopic group. However, the postoperative hospital stay [(12.34±3.46) vs. (15.10 ± 4.48) d], bed rest time [(3.38±0.66) vs. (5.24±0.88) d], analgesic time [(4.31±0.90) vs. (6.22±1.26) d] and postoperative time to first feeding [(3.91±0.89) vs. (5.32±0.86) d] were significantly lower ( P<0.05). There were no significant differences in amounts of intraoperative bleeding, numbers of lymph node harvested and incidences of postoperative complications between groups ( P>0.05). Conclusion:Under the premise of strictly indications, laparoscopic radical resection of hilar cholangiocarcinoma was safe and feasible, and had certain advantages in promoting the rapid recovery of patients.

Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. Dysmorphic neurons are the major histopathological feature of type II FCD, but their role in seizure genesis in FCD is unclear. Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients. Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in type II FCD, including an enlarged soma, aberrant dendritic arbors, increased current injection for rheobase action potential firing, and reduced action potential firing frequency. Intriguingly, the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na⁺-K⁺-Cl^- cotransporter. In addition, we found a depolarizing shift of the GABA reversal potential in the CamKII-cre::PTEN^flox/flox mouse model of drug-resistant epilepsy, suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons. Thus, imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in type II FCD.
Animals ; Drug Resistant Epilepsy/surgery* ; Epilepsy/pathology* ; Malformations of Cortical Development/pathology* ; Malformations of Cortical Development, Group I ; Mice ; Neurons/pathology* ; Seizures/pathology*

Objective:To observe the changes of insulin secretion in the early stage of severe scald in rats, and to explore its signal transduction mechanism.Methods:Twenty-four male Wistar rats aged 7 weeks were divided into sham injury alone (SIA) group, sham injury+ BPV (HOpic) (SIB) group, scald alone (SA) group, and scald+ BPV (HOpic) (SB) group using the random number table, with 6 rats in each group. Full-thickness scald of 50% total body surface area was inflicted in rats of SA and SB groups by a 6-s immersion of the abdomen and a 12-s immersion of the back in 94 ℃ hot water. Rats in SIA and SIB groups received sham injuries through immersion of the back and abdomen in 37 ℃ warm water for 6 and 12 seconds respectively. From 0 (immediately) to 2 day (s) after injury, the rats in groups SB and SIB were intraperitoneally injected with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway enhancer BPV (HOpic) solution (0.5 mg/mL) at the dosage of 0.6 mg/kg once a day, and the rats in groups SA and SIA were intraperitoneally injected with the same volume of dimethyl sulfoxide once a day. At post injury hour (PIH) 72, the tail blood of rats was sampled for measuring fasting blood glucose (FBG) with a glucometer, and the pancreatic tissue samples of rats was harvested for observing the pathological manifestations of islets by hematoxylin-eosin staining, counting the docked granules per 10 μm membrane of islet beta cells and calculating the proportion of insulin vesicles through the observation of the ultrastructure of islet beta cells by transmission electron microscope, and detecting the phosphorylation level of Akt in the pancreatic PI3K/Akt signaling pathway by Western blotting. Data were statistically analyzed with one-way analysis of variance and least significant difference test.Results:(1) At PIH 72, the rat FBG levels in SIA and SIB groups were normal and similar ( P>0.05). Compared with the levels of those two groups, the rat FBG level in SA group was increased significantly ( P<0.01), while the level in SB group showed no obvious change ( P>0.05). Compared with that in SA group, the rat FBG level in SB group was decreased significantly ( P<0.01). (2) At PIH 72, the morphology of rat islets was complete and the islet cells distributed regularly in SIA and SIB groups. Compared with those in SIA and SIB groups, the morphology of rat islets was incomplete, the insulin vesicles in islets were common, the islet cells distributed irregularly, and the cytoplasm of some islet beta cells was lightly stained or translucent in SA group; the morphology of islets in SB group did not change obviously. Compared with those in SA group, the morphology of islets was comparatively complete, the insulin vesicles in islets were less common, the islet cells distributed comparatively regularly, and the lightly stained or translucent cytoplasm of islet beta cells was less in SB group. (3) At PIH 72, the number of docked granules per 10 μm membrane of rat islet beta cells and the proportion of insulin vesicles in SIA and SIB groups were similar ( P>0.05). Compared with those in SIA and SIB groups, the number of docked granules per 10 μm membrane of rat islet beta cells in SA group was decreased significantly ( P<0.01), while the proportion of insulin vesicles was increased significantly ( P<0.01); the number of docked granules per 10 μm membrane of rat islet beta cells in SB group was obviously decreased ( P<0.05), while the proportion of insulin vesicles did not change obviously ( P>0.05). Compared with those in SA group, the number of docked granules per 10 μm membrane of rat islet beta cells in SB group was significantly increased ( P<0.01), while the proportion of insulin vesicles was significantly decreased ( P<0.01). (4) At PIH 72, the phosphorylation levels of Akt in SIA, SIB, SA, and SB groups were 0.91±0.03, 0.98±0.03, 0.78±0.08, and 0.87±0.08, respectively. Compared with that in SIA group, the phosphorylation level of Akt was increased obviously in SIB group ( P<0.05) but was decreased significantly in SA group ( P<0.01), while the level in SB group did not change obviously ( P>0.05). Compared with the level in SIB group, the phosphorylation levels of Akt in SA and SB groups were decreased significantly ( P<0.01). Compared with that in SA group, the phosphorylation level of Akt in SB group was increased significantly ( P<0.05). Conclusions:At the early stage post severe scald in rats, the activity of the pancreatic PI3K/Akt signaling pathway and the function of insulin secretion are reduced. Improving the activity of the pancreatic PI3K/Akt signaling pathway in rats can ameliorate the function of insulin secretion and recover the physiological level of blood glucose.

Objective To investigate the efficacy of calf self weight traction reduction combined with locking plate fixation for the treatment of intertrochanteric fractures in the elderly.Methods A retrospective case series study was conducted on the clinical records of 174 elderly patients with the modified Evans Ⅰ-Ⅲ types of fresh intertrochanteric fractures treated with locking plate from January 2012 to December 2015.According to treatment method,the patients were assigned to traction bed reduction with locking plate fixation (Group A,62 patients) and calf self weight traction reduction with locking plate fixation (Group B,112 patients).Group A comprised 32 males and 30 females,with age range of 65-91 years [(72.47 ± 6.35) years].Group B comprised 68 males and 44 females,with age range of 65-95 years [(73.23 ± 6.05) years].The time of reduction,operation time,incision length,intraoperative blood loss,frequency of fluoroscopy,postoperative drainage volume,hospital stay,postoperative weightbearing standing time or walking time (ambulation time),surgical complications,and fracture healing were recorded.Harris and modified Barthel index score in Chinese (MBI-C) were used to evaluate the functional recovery of hip joint.Results All patients were followed up for 5-61 months (mean,15 months),and noted with fracture healing.The time of reduction in Group A was (13.27 ± 3.03) minutes,longer than that in Group B (0 minute) (P ＜0.05).The operation time in Group A was (63.63 ± 13.90)minutes,longer than that in Group B [(59.62 ± 8.38) minutes] (P ＜ 0.05).Fluoroscopy in Group A was (5.35 ± 2.36) times,more than (4.28 ± 3.11) times in Group B (P ＜ 0.05).There were no significant differences in the incision length,intraoperative blood loss,postoperative drainage volume,ambulation time,fracture healing time,Harris score,and MBI-C index between the two groups (P ＞0.05).There were no significant differences in the postoperative complications such as deep venous thrombosis,pulmonary infection,incisional infection,urinary tract infection,delirium,bed sores,cardiac insufficiency,electrolyte disturbance,and postoperative plate rupture between the two groups (P＞0.05).The incidence of deep vein thrombosis was 9.7％ (6/62) in Group A,and 4.5％ (5/112) in Group B (P ＞0.05).No screw fracture,nail and plate combination failure,bone nonunion,or screw cut out of the femoral head were observed in both groups.Conclusions For the modified Evans Ⅰ-Ⅲ types of intertrochanteric fractures,both traction bed reduction and calf weight reduction with locking plate have equivalent efficacy.However,the latter method has advantages of shorter reduction and operation time and less intraoperative X-ray exposure,and hence is worthy of clinical application.

Objective To systematically evaluate the postoperative complications following open reduction and internal fixation combined with vascularized bone flap graft versus only reduction and internal fixation for femoral neck fractures.Methods CNKI,Wan Fang Chinese database,Pubmed,EMBASE and Google Scholar English database were searched for the randomized controlled trials from January 1,2000 through October 31,2017 which compared open reduction and internal fixation combined with vascularized bone flap graft (combined surgery group) with only reduction and internal fixation (simple surgery group) for femoral neck fractures.The data concerning postoperative nonunion and avascular necrosis of the femoral head were extracted.The 2 surgical treatments of the patients with femoral neck fracture were compared in terms of the 2 complications.Statistical analyses were conducted using software Stata 12 by relative risk (RR) and corresponding 95％ confidence intervals (95％ CI).Results According to our inclusion and exclusion criteria,a total of 23 studies were included,involving 2,162 cases (1,048 cases receiving combined surgery and 1,114 cases simple surgery).The Meta analyses showed that the fracture nonunion rate for the combined surgery group was significantly lower than that for the simple surgery group [RR =0.27,95％ CI(0.19,0.38),P ＜ 0.001] and the rate of avascular necrosis was also significantly lower for the former than for the latter [RR =0.31,95 ％ CI(0.24,0.42),P ＜ 0.001].Conclusion In the treatment of femoral neck fractures,open reduction and internal fixation combined with vascularied bone graft may lead to lower rates of nonunion and avascular necrosis of the femoral head than simple open reduction and internal fixation.

Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Lymphoma ; drug therapy ; Recombinant Proteins ; therapeutic use ; Retrospective Studies