Objective To construct a risk assessment scale for postoperative delirium(POD)in elderly patients undergoing hip and knee joint replacement and evaluate the effect.Methods A total of 474 elderly patients undergoing hip and knee arthroplasty from March 2021 to May 2022 were collected as the training set,and a total of 153 the homogeneous patients from January 2022 to May 2022 were collected as the validation set.The patients were divided into two groups based on whether or not POD occurred:non-POD group and POD group.Risk factors of POD in the training set were analyzed by univariate analysis and multifactorial logistic regression.The consistency of the model was evaluated by Homser-Lemeshow goodness of fit test.The postoperative delirium risk assessment scale was established after the selected variables as-signed value according to OR value,and the predictive efficacy of the scale was evaluated by receiver oper-ating characteristic(ROC)curve.The patients in the training set and the validation set were divided into two groups according to the cut-off value:high-risk and low-risk.The incidence rate of POD with different risk stratification was calculated and the applicability of the risk assessment scale was evaluated.Results Fifty-eight patients(12.2%)with POD in the training set,and nineteen patients(12.4%)with POD in the validation set.Multifactor logistic regression showed that age≥85 years,ASA physical status Ⅲ or Ⅳ,the mini-mental state examination(MMSE)score≤24 points,preoperative sleep disorder,comorbid neu-rological disorders,use of general anesthesia,and non-use of dexmedetomidine were independent risk factors of POD.The POD risk assessment scale was then published based the seven risk factors.The ROC curve showed that the area under the curve(AUC)for this scale to predict the risk of POD was 0.956(95%CI 0.937-0.975),and the risk stratification was performed with a cut-off value of 44.5 points,which divided the patients into low-risk and high-risk.Compared with low-risk,the incidence rate of POD in high-risk patients group was significantly increased(P＜0.001).Conclusion A risk assessment scale based on the seven risk factors:age≥85 years,ASA physical status Ⅲ or Ⅳ,MMSE score≤24 points,preoperative sleep disorder,combined neurological disease,use of general anesthetic modality,and non-use of dexmedetomidine,can effectively identify elderly patients undergoing hip and knee replacement who are at high risk of developing POD.

Objective:To compare the clinical efficacy of ileocecal-preserving laparoscopic subtotal colectomy, antegrade peristaltic ascending colorectal anastomosis with antiperistalsis cecorectal anastomosis in the treatment of severe slow transit constipation.Methods:The clinical data of 42 patients with severe slow transit constipation undergoing surgery in Shulan (Hangzhou) Hospital from Jan 2016 to Oct 2021 were retrospectively analyzed. All 42 patients underwent ileocecal-preserving laparoscopic subtotal colectomy. Among them, 25 patients underwent antegrade peristaltic anastomosis of ascending colon and rectum, 17 patients underwent antiperistaltic anastomosis of cecum and rectum.Results:There was no significant difference in the operation time and hospitalization time between the two groups ( t=-0.464, P=0.645; t=0.010, P=0.992); Wexner constipation scores in both groups were significantly reduced at 6 and 12 months after surgery. There was no significant difference in the Wexner constipation scores ( t=-1.181, P=0.240; t=-1.717, P=0.090), the number of bowel movenents per day ( t=0.179, P=0.860; t=0.545, P=0.590) and stool shapes scores ( t=-0.316, P=0.750; t=0.447, P=0.660) between the two groups at 6 and 12 months after surgery. Gastrointestinal quality of life index scores in the antegrade peristaltic anastomosis group were significantly higher than those in the antiperistalsis anastomosis group at 6 and 12 months after surgery ( t=4.329, P<0.05; t=3.988, P<0.05), while abdominal pain scores were significantly lower than those in the antiperistalsis anastomosis group ( t=-4.386, P<0.05; t=-5.740, P<0.05). Conclusions:For patients with severe slow transit constipation, ileocecal-preserving laparoscopic subtotal colectomy has good surgical safety and near-to-medium-term clinical efficacy, whether it is antegrade peristaltic ascending colorectal anastomosis (the stump of the ascending colon is turned from front to back) or antiperistalsis cecorectal anastomosis. The antegrade peristaltic ascending colorectal anastomosis has lower abdominal pain score and better gastrointestinal quality of life than antiperistalsis cecorectal anastomosis, which should be recommended first. During the operation, the ileocolic mesentery should be fully separated to the root of mesentery and the ileocecal part should be turned from front to back to avoid the occurrence of mesenteric vascular torsion and small intestinal obstruction.

Glucagon-like peptide-1 (GLP-1) is expressed in retinal neurons, but its role in the retina is largely unknown. Here, we demonstrated that GLP-1 or the GLP-1 receptor (GLP-1R; a G protein-coupled receptor) agonist exendin-4 suppressed γ-aminobutyric acid receptor (GABAR)-mediated currents through GLP-1Rs in isolated rat retinal ganglion cells (GCs). Pre-incubation with the stimulatory G protein (G_s) inhibitor NF 449 abolished the exendin-4 effect. The exendin-4-induced suppression was mimicked by perfusion with 8-Br-cAMP (a cAMP analog), but was eliminated by the protein kinase A (PKA) inhibitor Rp-cAMP/KT-5720. The exendin-4 effect was accompanied by an increase in [Ca²⁺]_i of GCs through the IP₃-sensitive pathway and was blocked in Ca²⁺-free solution. Furthermore, when the activity of calmodulin (CaM) and CaM-dependent protein kinase II (CaMKII) was inhibited, the exendin-4 effect was eliminated. Consistent with this, exendin-4 suppressed GABAR-mediated light-evoked inhibitory postsynaptic currents in GCs in rat retinal slices. These results suggest that exendin-4-induced suppression may be mediated by a distinct G_s/cAMP-PKA/IP₃/Ca²⁺/CaM/CaMKII signaling pathway, following the activation of GLP-1Rs.

Antibodies, Monoclonal, Humanized/adverse effects* ; Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Myocarditis/drug therapy*

Mucormycosis is an infectious disease characterized by rapidly progressive vascular invasiveness, thrombosis and tissue necrosis, which could be potentially responsible for blocking the exudation of leukocytes to infection sites and affecting drug distribution. Glucose-regulated protein 78 (GRP78) is a key protein involved in regulating the invasiveness of Mucorales. Endoplasmic reticulum GRP78 is overexpressed under various stress conditions and transported to the cell membrane to become a cell surface receptor for Mucorales entering into vascular endothelial cells. This article reviewed the mechanisms and pathogenesis of GRP78-mediated host cell invasion and summarized the progress in related targeted drugs, aiming to provide reference for developing multi-target intervention against mucormycosis.

Objective: To explore the trichloroethylene-induced alteration of methylation on the promoter region of SET and related mechanisms in hepatic L-02 cells. Methods: L-02 cells were treated with different concentrations of TCE(0 mmol/L, 1 mmol/L, 2 mmol/L, 4 mmol/L, 8 mmol/L) for 24 h. The genomic DNA were then extracted and modified by bisulfite sodium. The DNA methylation was then analyzed using bisulfite sequencing PCR (BSP). Results: The overall methylation on promoter region of SET was decreased along with the increased concentrations of TCE in hepatic L-02 cells. Moreover, 73 CpG islands were found abnormally altered, among which 9 were predicted in transcriptional factor binding regions. Conclusion The decreased levels of CpG islands in the transcriptional factor binding region may contribute to the elevation of SET in TCE-induced hepatotoxicity.

Recent clinical research shows that a prolonged infusion administration strategy of β-lactam antibiotics compared with intermittent infusion,may improve microbiologic and clinical cure,especially when pathogens demonstrate higher minimum inhibitory concentrations (MIC).This article reviews β-lactam pharmacodynamic background and advantages,clinical benefits and risks,clinical efficacy and potential drawbacks of prolonged infusion β-lactam antibiotics.

OBJECTIVETo compare the clinical effects and radiographic outcomes of mini-open trans-spatium intermuscular and percutaneous short-segment pedicle fixation in treating thoracolumbar mono-segmental vertebral fractures without neurological deficits.

METHODSFrom August 2009 and August 2012, 95 patients with thoracolumbar mono-segmental vertebral fractures without neurological deficits were treated with short-segment pedicle fixation through mini-open trans-spatium intermuscular or percutaneous approach. There were 65 males and 30 females, aged from 16 to 60 years old with an average of 42 years. The mini-open trans-spatium intermuscular approach was used in 58 cases (group A) and the percutaneous approach was used in 37 cases (group B). Total incision length, operative time, intraoperative bleeding, fluoroscopy, hospitalization cost were compared between two groups. Visual analog scale (VAS) and radiographic outcomes were compared between two groups.

RESULTSAll patients were followed up from 12 to 36 months with an average of 19.6 months. No complications such as incision infection, internal fixation loosening and breakage were found. In group A, fluoroscopy time was short and hospitalization cost was lower than that of group B (P<0.05). But the total incision length in group B was smaller than that of group A (P<0.05). There was no significant differences in operative time, intraoperative bleeding, postoperative VAS and radiographic outcomes between two groups (P>0.05). Postoperative VAS and radiographic outcomes were improved than that of preoperative (P<0.05).

CONCLUSIONThe mini-open trans-spatium intermuscular and percutaneous short-segment pedicle fixation have similar clinical effects and radiographic outcomes in treating thoracolumbar mono-segmental vertebral fractures without neurological deficits. However, in this study, the mini-open trans-spatium intermuscular approach has a short learning curve and more advantages in hospitalization cost and intraoperative radiation exposure times, and is recommendable.

Adolescent ; Adult ; Female ; Fluoroscopy ; Fracture Fixation, Internal ; methods ; Humans ; Lumbar Vertebrae ; injuries ; surgery ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; Spinal Fractures ; surgery ; Thoracic Vertebrae ; injuries ; surgery ; Visual Analog Scale

Objective To investigate the chemical preventive effect of matrine on ethyl nitrate nitroguanidine nitrate induced gastric cancer in rats. Methods 100 male Wistar rats were selected and randomly divided into four groups,each had 25 rats ,treated with different drugs respectively.Rats in the negative control group (group A)freely drunk water;each rat in gastric carcer model group (group B)drunk ethyl nitrate nitroguanidine nitrate (ENNG)1.5 mg/d by themselves;gastric cancer model rats of experimental group (group C)drunk matrine 150 mg/(kg · d)ethyl nitrate nitroguanidine nitrate (ENNG)150mg/(kg·d)by themselves;negative control group (group D)rats drunk matrine for injection 150 mg/(kg·d)by themselves.Rats were killed after 24 weeks,rats were observed on gastric mucosa change by naked eye and microscope ,and detected proliferating cell nucleus antigen (PCNA)of stomach tissue ,levels of serum transforming growth factorβ1 (TGF-β1 )and B cell lymphoma/leukemia-2 (Bcl-2).Results Canceration rate [64.00% (16/25)]of the rat gastric mucosa in Group B was significantly higher than that in group C [12.00% (3/25)],and the difference was statistically significant (P<0.05 );PCNA,TGF-β1 and the Bcl-2 level of rats in group C was lower than those in group B,and the difference was statistically significant (P<0.05 );after raising 24 weeks,change rate of gastric mucosa atrophy and hyperplasia in group B were significantly higher than those of group C,and the difference was statistically significant (P<0.05 );after raising 24 weeks,there was no cancerous changes on gastric mucosa in group A and D ,and the change of gastric mucosa atrophy and hyperplasia had no obvious difference,there was no statistically significant difference.Conclusion Matrine could inhibit rat gastric cancer induced by ENNG by lowering PCNA,TGF-β1 and the Bcl-2 levels,which provides evidence for the potential chemical preventive effect on human gastric cancer.

BACKGROUNDPodocyte apoptosis is recently indicated as an early phenomenon of diabetic nephropathy. Pancreatic β-cells exposed to saturated free fatty acid palmitate undergo irreversible endoplasmic reticulum (ER) stress and consequent apoptosis, contributing to the onset of diabetes. We hypothesized that palmitate could induce podocyte apoptosis via ER stress, which initiates or aggravates proteinuria in diabetic nephropathy.

METHODSPodocyte apoptosis was detected by 4',6-diamidio-2-phenylindole (DAPI) stained apoptotic cell count and Annexin V-PI stain. The expressions of ER molecule chaperone glucose-regulated protein 78 (GRP78), indicators of ER-associated apoptosis C/EBP homologous protein (CHOP), and Bcl-2 were assayed by Western blotting and real-time PCR. GRP78 and synaptopodin were co-localized by immunofluorescence stain.

RESULTSPalmitate significantly increased the percentage of cultured apoptotic murine podocytes time-dependently when loading 0.75 mmol/L (10 hours, 13 hours, and 15 hours compared with 0 hour, P < 0.001) and dose-dependently when loading palmitate ranging from 0.25 to 1.00 mmol/L for 15 hours (compared to control, P < 0.001). Palmitate time-dependently and dose-dependently increased the protein expression of GRP78 and CHOP, and decreased that of Bcl-2. Palmitate loading ranging from 0.5 to 1.0 mmol/L for 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to control (P < 0.001), with the maximum concentration being 0.75 mmol/L. Palmitate 0.5 mmol/L loading for 3 hours, 8 hours, and 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to 0 hour (P < 0.001), with the maximum effect at 3 hours. Confocal microscopy demonstrated that GRP78 expression was significantly increased when exposed to 0.5 mmol/L of palmitate for 8 hours compared to control.

CONCLUSIONPalmitate could induce podocyte apoptosis via ER stress, suggesting podocyte apoptosis and consequent proteinuria caused by lipotoxic free fatty acid could be ameliorated by relief of ER stress.

Apoptosis ; drug effects ; Cells, Cultured ; Endoplasmic Reticulum Stress ; physiology ; Heat-Shock Proteins ; analysis ; physiology ; Humans ; Insulin Resistance ; Palmitic Acid ; pharmacology ; Podocytes ; drug effects ; pathology