This study aims to explore whether Albiziae Cortex-Tribuli Fructus can exert an anti-hepatic fibrosis effect by regulating the nuclear factor E2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)/cysteine protease-1(caspase-1) pathway and analyze its potential mechanism. In the in vivo experiment, a mouse model of hepatic fibrosis was established by subcutaneous injection of carbon tetrachloride. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), collagen type Ⅳ(ColⅣ), laminin(LN), procollagen type Ⅲ(PCⅢ), and hyaluronic acid(HA) in the serum of mice were measured using a fully automated biochemical analyzer and ELISA. Hematoxylin and eosin(HE) and Masson staining were used to observe inflammation and collagen fiber deposition in the liver tissue. Western blot and RT-qPCR were employed to detect the protein and mRNA expression of collagen type Ⅰ(collagen Ⅰ), α-smooth muscle actin(α-SMA), Nrf2, NLRP3, gasdermin D(GSDMD), and caspase-1 in the hepatic tissue. In the in vitro experiment, human hepatic stellate cells(HSC-LX2) were pretreated with Nrf2 agonist or inhibitor, followed by the addition of blank serum, AngⅡ + blank serum, and AngⅡ + Albiziae Cortex-Tribuli Fructus-containing serum for intervention. Western blot was used to detect the protein expression of Nrf2, NLRP3, GSDMD, caspase-1, α-SMA, GSDMD-N, and apoptosis-associated speck-like protein(ASC) in cells. DCFH-DA fluorescence probe was used to detect the cellular ROS levels. The results from the in vivo experiment showed that, compared with the model group, Albiziae Cortex-Tribuli Fructus significantly reduced the serum levels of AST, ALT, ColⅣ, LN, PCⅢ, and HA, reduced the infiltration of inflammatory cells and collagen fiber deposition in the liver tissue, significantly upregulated the protein and mRNA expression of Nrf2 in the liver tissue, and significantly downregulated the protein and mRNA expression of collagen I, α-SMA, NLRP3, GSDMD, and caspase-1 in the liver tissue. The results from the in vitro experiment showed that Nrf2 activation decreased the protein expression of NLRP3, GSDMD, caspase-1, α-SMA, GSDMD-N, ASC, and ROS levels in HSC-LX2, while Nrf2 inhibition showed the opposite trend. Furthermore, Albiziae Cortex-Tribuli Fructus-containing serum directly decreased the expression of the above proteins and ROS levels. In conclusion, Albiziae Cortex-Tribuli Fructus can effectively improve hepatic fibrosis, and its mechanism of action may involve inhibiting pyroptosis through the regulation of the Nrf2/NLRP3/caspase-1 pathway.
Animals ; NF-E2-Related Factor 2/genetics* ; Liver Cirrhosis/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 1/genetics* ; Male ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Signal Transduction/drug effects* ; Humans ; Liver/metabolism* ; Mice, Inbred C57BL ; Plant Extracts ; Tribulus

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

OBJECTIVE To create a highly effective algorithm for automatically generating easily confused drug catalogs （ECDC）， as well as to develop a management system for ECDC based on this algorithm， in order to improve the management efficiency of ECDC. METHODS This study， based on Levenshtein distance algorithm， delved deeply into the automatic identification mechanism of easily confused drugs and the screening method for determining similarity thresholds， ultimately leading to the development of an algorithm for automatically generating ECDC. Besides a management system was designed and developed， using SQL Server 2008 R2 Express as the data storage platform and Visual Basic.NET as the programming language. RESULTS The similarity threshold δ played a crucial role in the algorithm for automatically generating ECDC. As the value of δ gradually increased， the total count of easily confused drugs decreased gradually， while the count of drug groups exhibited a pattern of initially increasing and then decreasing. Practically， ECDC could be created using either the generic or varietal names of drugs， with corresponding similarity thresholds of 0.75 and 0.83. Furthermore， ECDC management system had significantly reduced the time required to establish a catalog from about one week to less than one hour， resulting in a substantial enhancement in work efficiency. CONCLUSIONS The algorithm used to automatically generate ECDC is highly efficient and rapid， offering robust technical assistance for the management of easily confused drugs. Implementing the ECDC system can greatly reduce the time cost related to building and maintaining the catalogs， thus significantly improving the efficiency of managing ECDC.

BACKGROUND:Early identification of patients requiring ventilator support will be beneficial for the outcomes of botulism.The present study aimed to establish a new scoring system to predict mechanical ventilation(MV)for botulism patients. METHODS:A single-center retrospective study was conducted to identify risk factors associated with MV in botulism patients from 2007 to 2022.Univariate analysis and multivariate logistic regression analysis were used to screen out risk factors for constructing a prognostic scoring system.The area under the receiver operating characteristic(ROC)curve was calculated. RESULTS:A total of 153 patients with botulism(66 males and 87 females,with an average age of 43 years)were included.Of these,49 patients(32.0%)required MV,including 21(13.7%)with invasive ventilation and 28(18.3%)with non-invasive ventilation.Multivariate analysis revealed that botulinum toxin type,pneumonia,incubation period,degree of hypoxia,and severity of muscle involvement were independent risk factors for MV.These risk factors were incorporated into a multivariate logistic regression analysis to establish a prognostic scoring system.Each risk factor was scored by allocating a weight based on its regression coefficient and rounded to whole numbers for practical utilization([botulinum toxin type A:1],[pneumonia:2],[incubation period≤1 day:2],[hypoxia<90%:2],[severity of muscle involvement:grade II,3;grade III,7;grade IV,11]).The scoring system achieved an area under the ROC curve of 0.82(95%CI 0.75-0.89,P<0.001).At the optimal threshold of 9,the scoring system achieved a sensitivity of 83.7%and a specificity of 70.2%. CONCLUSION:Our study identified botulinum toxin type,pneumonia,incubation period,degree of hypoxia,and severity of muscle involvement as independent risk factors for MV in botulism patients.A score≥9 in our scoring system is associated with a higher likelihood of requiring MV in botulism patients.This scoring system needs to be validated externally before it can be applied in clinical settings.

Objective:With the in-depth study of complement dysregulation,glomerulonephritis with dominant C3 has received increasing attention,with a variety of pathologic types and large differences in symptoms and prognosis between pathologic types.This study analyzes the clinical,pathological,and prognostic characteristics of different pathological types of glomerulonephritis with dominant C3,aiming to avoid misdiagnosis and missed diagnoses. Methods:The clinical,pathological,and follow-up data of 52 patients diagnosed as glomerulonephritis with dominant C3 by renal biopsy from June 2013 to October 2022 were retrospectively analyzed.According to the clinical feature and results of pathology,15 patients with post-infectious glomerulonephritis(PIGN)and 37 patients with of non-infectious glomerulonephritis(N-PIGN)were classified.N-PIGN subgroup analysis was performed,and 16 patients were assigned into a C3-alone-deposition group and 21 in a C3-dominant-deposition group,or 27 in a C3 glomerulopathy(C3G)group and 10 in a non-C3 nephropathy(N-C3G)group. Results:The PIGN group had lower creatinine values(84.60 μmol/L vs 179.62 μmol/L,P= 0.001),lower complement C3 values(0.36 g/L vs 0.74 g/L,P<0.001)at biopsy,and less severe pathological chronic lesions compared with the N-PIGN group.In the N-PIGN subgroup analysis,the C3-dominant-deposition group had higher creatinine values(235.30 μmol/L vs 106.70 μmol/L,P=0.004)and higher 24-hour urine protein values(4 025.62 mg vs 1 981.11 mg,P=0.037)than the C3-alone-deposition group.The prognosis of kidney in the PIGN group(P=0.049),the C3-alone-deposition group(P=0.017),and the C3G group(P=0.018)was better than that in the N-PIGN group,the C3-dominant-deposition group,and the N-C3G group,respectively. Conclusion:Glomerulonephritis with dominant C3 covers a variety of pathological types,and PIGN needs to be excluded before diagnosing C3G because of considerable overlap with atypical PIGN and C3G;in addition,the deposition of C1q complement under fluorescence microscope may indicate poor renal prognosis,and relevant diagnosis,treatment,and follow-up should be strengthened.

ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

Objective To investigate the effect of early postoperative abnormal blood glucose on the short-term prognosis of non-small cell lung cancer(NSCLC),and to analyze the clinical characteristics and risk factors related to poor early prognosis.Methods A total of 897 patients with NSCLC who underwent thoracoscopic surgery in Huadong Hospital,Fudan University from Jan 2020 to Aug 2021 were divided into hyperglycemia(HG)group(>7.8 mmol/L)and normal blood glucose(NG)group(≤7.8 mmol/L and≥3.9 mmol/L)according to the early postoperative blood glucose values.Additionally,the patients were divided into higher blood glucose fluctuation group(≥4 mmol/L)and the group with lower blood glucose fluctuation(<4 mmol/L)basing on the fasting blood glucose.Using Logistic regression models,column line charts,ROC curves and other methods,we aimed to clarify the impact of early postoperative blood glucose abnormalities on short-term prognosis,explore clinical characteristics associated with poor short-term outcomes,identify other high-risk factors,and establish relevant risk prediction models.Results Compared with the NG group,the incidence of postoperative pneumonia,thromboembolism,ICU admission rate,total length of hospital stay and hospital cost were significantly higher in the HG group(P<0.05).Higher blood glucose fluctuation group had a greater risk of ICU admission(P=0.003).Logistic regression analysis showed that age,preoperative fasting glucose,white blood cell count and cytokeratin 19 fragment antigen 21-1(CYFRA21-1)were risk factors for postoperative hyperglycemia(P<0.05).Contrary to the effect of BMI,diabetes,male patients,higher blood glucose fluctuation,white blood cell count and age were the risk factors for postoperative adverse events(P<0.05).The AUC of the column line chart model was 0.661(95%CI:0.624-0.698),indicating good discriminative ability for predicting poor short-term prognosis postoperatively.Calibration curves also demonstrated good consistency between predicted and actual probabilities.Conclusion Early postoperative blood glucose fluctuations independently impact the short-term prognosis of thoracoscopic NSCLC patients.Blood glucose combined with gender,BMI,white blood cell count,age and diabetes history can serve as predictive factors for poor short-term prognosis postoperatively.Additionally,a column line chart constructed based on these factors may aid clinicians in early intervention for NSCLC patients with indications.

Objective To assess short-and long-term changes in the upper airway,natural head position and hyoid bone position in skeletal Class Ⅲ patients after bimaxillary surgery.Methods In this retrospective study,the cone-beam computed tomography(CBCT)of skeletal Class Ⅲ patients was taken before surgery(T0),3 months after surgery(T1)and 2 years after surgery(T2).Three-dimensional images were created to assess postoperative changes and the correlation between the upper airway,natural head posi-tion and hyoid bone was analyzed.Results Thirty skeletal Class Ⅲ patients(13 men and 17 women)who underwent bimaxillary sur-gery with a mean(SD)age of 21 years(a range of 17-30 years)were evaluated.A significant decrease was observed in the volume of palatopharynx,glossopharynx and total airway after T1 and T2.There was a significant correlation between changes in the position of the mandible and changes in the volume of the upper airway(P＜0.05).The NSL/OPT angle and the NSL/CVT angle were greater after Tl and T2.The change in the NSL/CVT angle was positively correlated with the change in palatopharyngeal and glossopharyngeal volume(P＜0.05).Conclusion Bimaxillary surgery may cause a decrease in upper airway volume,an increase in the cranio-cervical angle,and a downward and backward movement of the hyoid bone.Changes in the cranio-cervical angle may cause changes in the upper air-way.

Objective To evaluate the feasibility of emergency percutaneous coronary intervention(PCI)with extracorporeal membrane oxygenation(ECMO)support in critically ill patients with acute myocardial infarction(AMI)and cardiogenic shock(CS).Methods Retrospective analysis of clinical data of AMI combined with CS patients admitted to the department of emergency of the Second Hospital of Hebei Medical University from December 2018 to December 2021,including gender,age,body mass index(BMI),past history(smoking,coronary heart disease,arrhythmia,diabetes,hypertension,hyperlipidemia,cerebrovascular disease);acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score,highest vasoactive-inotropic score(VIS)within 24 hours of admission,the worst auxiliary examination values within 24 hours after admission:blood lactic acid(Lac),arterial partial pressure of oxygen(PaO2),cardiac troponin I(cTnI),alanine aminotransferase(ALT),total bilirubin(TBil),creatinine(Cr),serum potassium,left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF)],presence of malignant arrhythmia or cardiac arrest during emergency PCI,completion of PCI,and the 30-day prognosis,etc.Patients were divided into an ECMO group and a non-ECMO group based on whether ECMO was applied,to analyze differences in the above indicators between the two groups.Results There were no statistically significant differences between the ECMO group and the non-ECMO group in terms of gender,age,BMI,past history,APACHEⅡ,VIS and the worst auxiliary examination value within 24 hours after admission.The incidence of malignant arrhythmia or cardiac arrest events and 30-day mortality rate during emergency PCI in the ECMO group were significantly lower than those in the non-ECMO group[the incidence of malignant arrhythmia or cardiac arrest during emergency PCI was 17.9％(7/39)vs.45.0％(9/20),and the 30-day mortality was 46.2％(18/39)vs.75.0％(15/20),both P<0.05].The completion rate of PCI in the ECMO group was significantly higher than that in the non-ECMO group[100.0％(39/39)vs.80.0％(16/20),P<0.05].Conclusions For critically ill patients with AMI combined with CS,ECMO support can reduce the risk of malignant arrhythmia or cardiac arrest during emergency PCI,increase the completion rate of PCI,and reduce the 30-day mortality.With the support of the ECMO team,ECMO support emergency PCI is feasible.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.