OBJECTIVE To investigate the effects and mechanisms of Buyang huanwu decoction （BYHWD） and its active fractions in ameliorating non-alcoholic fatty liver disease. METHODS BYHWD and its effective fractions obtained through ethanol precipitation， as well as 30% ethanol， 50% ethanol， and 75% ethanol fractions （namely， the CC effective fraction， 30YC effective fraction， 50YC effective fraction， and 75YC effective fraction）， were prepared. These preparations were administered to rats via intragastric administration to prepare corresponding drug-containing serum （blank serum and simvastatin-containing serum were prepared using the same protocol）. Human L02 hepatocytes were divided into control group， model group， simvastatin-containing serum group， BYHWD-containing serum group， CC-containing serum group， 30YC-containing serum group， 50YC-containing serum group， and 75YC-containing serum group. Except for the control group， other groups were given 0.2 mol/L oleic acid for 24 h to induce a lipid accumulation model， and then intervened with 20% drug-containing serum/blank serum for 24 h. The lipid deposition in cells was observed， and the proportion of lipid droplet area was calculated； the levels of triglycerides （TG） and indicators of oxidative stress [malondialdehyde （MDA）， superoxide dismutase （SOD）] as well as liver function [alanine amino- transferase （ALT）， aspartate amino-transferase （AST）] in cells were detected； protein and mRNA expressions of AMP-activated protein kinase （AMPK）/sterol regulatory element-binding protein-1 （SREBP-1）/glycerol-3-phosphate acyltransferase （GPAT） signaling pathway were also measured. RESULTS Compared with the control group， cells in the model group exhibited severe cellular steatosis， with a significantly increased proportion of lipid droplet area， as well as the elevated levels of TG， ALT， AST， and MDA in cells， along with significantly up-regulated mRNA and protein expression levels of SREBP-1 and GPAT （P＜0.05）. The level of SOD， mRNA expression of AMPK， as well as the protein phosphorylation level of AMPK were decreased significantly （P＜0.05）. Compared with the model group， cellular steatosis was alleviated in all drug-containing serum groups， and the levels of most of the aforementioned quantitative indicators were significantly reversed （P＜0.05）. CONCLUSIONS BYHWD and its active fractions can exert a therapeutic effect on improving non-alcoholic fatty liver disease by regulating the AMPK/SREBP-1/GPAT signaling pathway， inhibiting oxidative stress responses， and reducing lipid deposition.

BACKGROUND: The proportion of patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is relatively high in China. However, these patients currently lack significant benefits from available neoadjuvant treatment options. This study aims to explore the potential application value of neoadjuvant targeted therapy by evaluating its efficacy and safety in patients with EGFR-mutant resectable lung adenocarcinoma. METHODS: A multicenter retrospective study was used to analyze the treatment effect of patients with stage IIA-IIIB EGFR-mutant lung adenocarcinoma who underwent surgical resection after receiving neoadjuvant targeted therapy from July 2019 to October 2024. RESULTS: A total of 24 patients with EGFR-mutant lung adenocarcinoma from three centers were included in this study. All patients successfully underwent surgery and achieved R0 resection of 100.0%. The objective response rate (ORR) was 83.3% (20/24) . The major pathologic response (MPR) rate was 37.5% (9/24), with 2 patients (8.3%) achieving pathological complete response (pCR). During neoadjuvant therapy, 13 out of 24 patients (54.2%) experienced adverse events of grade 1-2, with no occurrences of ≥ grade 3. The most common treatment-related adverse events were rash (n=4, 16.7%), mouth sores (n=2, 8.3%), and diarrhea (n=2, 8.3%). The median follow-up time was 33.0 months, no deaths occurred in all patients, and the overall survival (OS) rate was 100.0%. The 1-year disease-free survival (DFS) rate was 91.1%, and the 2-year DFS rate remained at 86.2%. CONCLUSIONS The application of neoadjuvant targeted therapy in patients with EGFR-mutant resectable lung adenocarcinoma is safe and feasible, and is expected to become a highly promising neoadjuvant treatment option for the patients with EGFR-mutant lung adenocarcinoma.
Humans ; ErbB Receptors/metabolism* ; Male ; Female ; Middle Aged ; Adenocarcinoma of Lung/surgery* ; Neoadjuvant Therapy ; Lung Neoplasms/surgery* ; Aged ; Retrospective Studies ; Mutation ; Adult

Objective:To evaluate the accuracy and safety profile of a novel cuboid orientation-guided frontal horn ventriculostomy technique in patients with large hemispheric infarction (LHI).Methods:It was conducted a retrospective cohort study of 48 consecutive LHI patients who underwent the innovative ventriculostomy procedure between time period. Primary outcomes included procedural accuracy (success rates, catheter positioning) and safety indicators (complication rates).Results:All the punctured ventricles were small or of normal size. The success rate of puncture was 100%, the success rate of one-time puncture was 87% (42/48), and the average number of puncture was 1.13 times per case. The ratio of well-positioned tube heads was 87.5% (42/48). The actual angle of the inward deviation of the puncture ranged from -2o to 5o, with an average of 0o±0.3o. The depth of puncture was 7.0-8.0 cm ( 7.3±0.3) cm. The incidence of bleeding around the puncture path was 1.3% (2/48 ) and no massive bleeding occurred. At the 6-month follow-up, one case (2.94%) among the 34 survivors had epilepsy.Conclusions:The cuboid orientation-guided frontal horn ventriculostomy technique demonstrates exceptional procedural accuracy and an excellent safety profile in LHI patients, with high first-pass success rates (87.5%) and minimal complications (4.2% minor hemorrhage). These findings support its clinical adoption for this patient population.

The basement membrane is a specialized extracellular matrix between the epithelium and the mesenchyme.In stratified epithelium,only the basal cells in contact with the basement membrane exhibit the apical-basal polarity,whereas the epithelial cells do being not in contact with the basement membrane do not exhibit the apical-basal polarity.The basement membrane plays an important role in epithelial cell polarization.It is an important extracellular matrix(ECM)structure in the multicellular organisms,is situated between the epithelium and the mesenchyme,and is produced jointly by the epithelial cells and mesenchymal cells.Its components mainly include Laminin,type Ⅳ collagen(Col-Ⅳ),nidogen(NDG),and heparan sulfate proteoglycans(HSPG),and each component plays the different role in influencing the epithelial cell polarity.The network scaffold formed by Col-Ⅳ and Laminin is the main structure of the basement membrane,and the integrity of the structure affects the epithelial cell polarization.This review summarizes the composition and structure of the basement membrane,focuses on its role in epithelial cell polarization and its mechanism,and compiles the current status of biomimetic basement membrane materials that promotes the epithelial cell polarization,and provides the theoretical foundation for further exploration of the establishment and maintenance of epithelial cell polarity.

Objective To investigate clinical characteristics and risk factors of different stages of urinary tract infection after kidney transplantation.Methods Clinical data of 209 kidney transplant recipients were retrospectively analyzed.According to time points of postoperative follow-up,all recipients were divided into 3 stages:within 1 month post-kidney transplantation,1-6 months post-kidney transplantation,and 7-12 months post-kidney transplantation.The incidence of urinary tract infection,urine culture results of recipients with urinary tract infection and drug resistance characteristics of common pathogens during different stages after kidney transplantation were analyzed.The strains of patients with recurrent urinary tract infection were identified.The risk factors of urinary tract infection and the effect of urinary tract infection on renal allograft function were analyzed.Results The urinary tract infection rate was 90.0％in the first stage,49.3％in the second stage and 22.5％in the third stage.The urinary tract infection rates of male recipients undergoing living-related organ donation in the second and third stages were lower than those of female recipients(both P＜0.05).Urine culture test yielded positive results in 60 cases,and 84 strains of pathogenic bacteria were detected,mainly Gram-negative bacteria,among which Klebsiella pneumoniae accounted for the highest proportion.Sixty-six recipients had recurrent urinary tract infection,and the detected pathogens included Klebsiella pneumoniae,Escherichia coli and Candida glabrata,etc.Univariate analysis showed that postoperative use of antithymocyte globulin was the risk factor for urinary tract infection in the first stage.Preoperative urinary tract infection and donor type were the risk factors for urinary tract infection in the second stage.Gender and age of the recipients were the risk factors for urinary tract infection in the third stage.Multivariate analysis revealed that postoperative use of antithymocyte globulin was the risk factor for urinary tract infection in the first stage.Gender and age of the recipients were the risk factors for urinary tract infection in the third stage(all P＜0.05).In the third stage,65 cases were cured and 38 cases were not cured.In the treated recipients,the serum creatinine level and white blood cell count were decreased after corresponding treatment than those before treatment(both P＜0.05).Conclusions Gram-negative bacteria are the main pathogens of urinary tract infection in kidney transplant recipients,and drug resistance is relatively high.Postoperative use of antithymocyte globulin,female and old age are the risk factors for urinary tract infection in kidney transplant recipients.

Objective:To explore the effect and safety of stereotactic aspiration of necrotic brain tissue for the patients≥61 years with malignant middle cerebral artery infarction (MMI).Methods:A total of 102 MMI patients aged≥61 years were enrolled retrospectively. All patients were subject to conservative medical treatment alone or in addition to stereotactic aspiration of necrotic brain tissue 24-72 hours after symptom onset. Perioperative outcomes and 6-month follow-up outcomes were observed and evaluated.Results:Baseline data characteristics were well balanced between the conservative treat group and aspiration group, except for the prevalence of hypertension. The incidence of early cerebral herniation (9.1% vs. 48.3%, χ2=17.843, P<0.001) and death (13.6% vs. 60.3%, χ2=22.707, P<0.001)in the aspiration group was significantly lower than that in the conservative group, and there was no significant difference in the incidence of cerebral hemorrhage ( P=0.726) and intracranial infection ( P=0.186) between the groups. At 6-month follow-up, compared with the conservative treatment group, the aspiration group had a higher proportion of favorable outcome (mRS 0-3) (38.6% vs. 3.4%, χ2 =20.438, P<0.001) and survival without severe disability (mRS 0-4) (68.2% vs. 22.4%, χ2=21.492, P<0.001). Comparison of clinical characteristics of favorable outcome (mRS 0-3) group and unfavorable (mRS 4-6) group showed that the proportion of patients treated with aspiration was significantly higher than that treated with medical therapy alone (89.5% vs. 10.5%, P<0.001). Multivariate logisitic regression used to adjust the confound factors such as atrial fibrillation, diabetes and smoking, the GCS and the NIHSS score of 24 hours after onset, etc, revealed that the treatment with aspiration was an independent association factor for the ratio of 6-month favorable outcome for the elderly patients with MMI ( OR=126.704, 95% CI: 7.236-2218.610, P<0.001). Conclusions:The stereotactic aspiration of necrotic brain tissue are effective and safe for the elderly patients with MMI.

Objective:To investigate the correlation between paroxysmal slow-wave events (PSWEs) and cerebral small vessel disease (CSVD) and CSVD-related cognitive impairment.Methods:Patients with CSVD visited Weihai Municipal Hospital from March 2021 to April 2022 were included, and sex- and age-matched healthy controls were recruited for cross-sectional analysis. The patients with CSVD were further divided into cognitive impairment group and non-cognitive impairment group. The self-developed Python script was used to detect the PSWE parameters in electroencephalogram records. Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to evaluate cognitive function. Multivariate logistic regression analysis was used to determine whether PWSE parameters were the independent related factors of CSVD and CSVD-related cognitive impairment. Multiple linear regression analysis was used to determine the correlation between the PSWE parameters and overall cognitive function (MoCA total score) in patients with CSVD. Results:A total of 76 patients with CSVD (including 41 patients with cognitive impairment and 35 patients without cognitive impairment) and 45 healthy controls were included. Compared with the healthy control group, PWSEs in the F3 (left frontal area) and O1 (left occipital area) regions of the CSVD group occurred more frequently and lasted longer (all P<0.05). Multivariate logistic regression analysis showed that the frequency (odds ratio [ OR] 1.080, 95% confidence interval [ CI] 1.023-1.140; P=0.005) and duration ( OR 1.006, 95% CI 1.001-1.011; P=0.023) of PWSEs in the left frontal area, as well as the frequency ( OR 1.052, 95% CI 1.010-1.095; P=0.014) and duration ( OR 1.003, 95% CI 1.000-1.006; P=0.028) of PWSEs in the left occipital region were the independent related factors for CSVD. The frequency ( OR 1.106, 95% CI 1.033-1.183; P=0.004) and duration ( OR1.010, 95% CI 1.003-1.017; P=0.004) of PWSEs in the left frontal area were the independent risk factors for cognitive impairment in patients with CSVD. Multiple linear regression analysis showed that the frequency ( β= –0.242, P=0.045) and duration ( β= –0.235, P=0.046) of PWSEs in the left frontal region were negatively correlated with the overall cognitive function score in patients with CSVD. Conclusions:The frequency and duration of PSWEs in some brain regions of patients with CSVD increase, and there is an independent correlation between PSWEs and cognitive impairment, suggesting that the damage of blood-brain barrier may participate in the pathogenesis of cognitive impairment in patients with CSVD.

Objective:To compare the efficacy of 3D-printed guide plate assisted versus freehand placement of cannulated screws for the treatment of Sanders type II and III calcaneal fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 29 patients with Sanders type II and III calcaneal fractures admitted to Chonggang General Hospital from June 2020 to October 2022. Among them, there were 18 males and 11 females, with an age range of 22-69 years [(40.1±11.5)years]. Nineteen patients were treated with individualized 3D-printed guide plate assisted placement of cannulated screws (3D-printed group) and 10 were treated with freehand placement of cannulated screws (freehand group). The surgical time, fluoroscopy times, postoperative 6-month calcaneal morphology (length, width, height, B?hler angle and Gissane angle), and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Maryland functional score assessed at 3, 6 months after operation and at the final follow-up were compared between the two groups. The incision healing and complications were observed.Results:The patients were followed up for 6-24 months [(11.3±2.5)months]. The surgical time and fluoroscopy times in the 3D-printed group were (53.4±9.1)minutes and (7.3±1.1)times, respectively, which were shorter than (90.2±16.0)minutes and (16.0±3.2)times in the freehand group (all P<0.01). At 6 months after operation, there was no significant difference in calcaneal length between the two groups ( P>0.05); the calcaneal width, height, B?hler angle and Gissane angle in the 3D-printed group [(34.0±1.8)mm, (47.2±1.6)mm, (27.8±1.0)°, (129.2±2.8)°] were superior than those in the freehand group [(37.5±2.0)mm, (43.0±2.7)mm, (25.8±1.5)°, (125.9±2.5)°] (all P<0.01). At 3, 6 months after operation and at the final follow-up, the values of AOFAS ankle-hindfoot score in the 3D-printed group [(72.2±2.3)points, (79.7±2.3)points, (86.5±4.4)points] were higher than those in the freehand group [(64.2±6.9)points, (73.4±4.2)points, (81.8±3.1)points] (all P<0.05); the values of Maryland score in the 3D-printed group [(71.4±7.7)points, (84.7±2.6)points, (91.5±2.5)points] were higher than those in the freehand group [(65.2±5.6)points, (79.1±3.8)points, (87.1±2.9)points] (all P<0.05). All surgical incisions were healed in stage I. In the 3D-printed group, there were no complications regarding infection, iatrogenic vascular or nerve injury, or fixation failure after surgery. In the freehand group, one patient with lateral sural cutaneous nerve injury was resolved spontaneously without specific treatment. Conclusion:Compared with freehand placement of cannulated screws, 3D-printed guide plate assisted placement of percutaneous placement has the advantages of shorter surgical time, fewer fluoroscopy times, lower reduction loss, better ankle joint function recovery, and less complications in treating Sanders type II and III calcaneal fractures.

Objective:To investigate the effect of the possibility of sleep-disordered breathing (SDB) as assessed by the four-variable score on the platelet function and the risk of stroke recurrence in patients with acute ischemic stroke.Methods:Patients with acute ischemic stroke admitted to the Department of Neurology, Weihai Municipal Hospital from January 2020 to January 2021 were enrolled prospectively. Main inclusion criteria: admission within 24 h of onset; National Institutes of Health Stroke Scale score ≤3; Receiving aspirin + clopidogrel dual antiplatelet therapy. All patients were divided into a high possibility group and a low possibility group of SDB according to the four-variable score. 7±2 d after dual antiplatelet therapy, PL-12 multi-parameter platelet function analyzer was used to detect the maximum aggregation rate (MAR). The patients were followed up for 6 months after discharge and the recurrence of ischemic stroke was observed. The mediating effect model was established with the high possibility of SDB as the independent variable, MAR as the intermediary variable and stroke recurrence as the dependent variable. Firstly, MAR as the dependent variable and high probability of SDB as the independent variable were analyzed by linear regression; then, a binary logistic regression analysis was performed with ischemic stroke recurrence as the dependent variable and the high probability of SDB and MAR as independent variables. Results:A total of 213 patients were enrolled in the study. The average age of the patients was 62.70 ± 10.04 years old. There were 146 male (68.5%) and 121 patients (56.8%) were in the high possibility group (56.8%). During the follow-up period, 24 patients (11.3%) had stroke recurrence. Univariate analysis showed that arachidonic acid (AA) induced MAR (MAR-AA) and adenosine diphosphate (ADP) induced the MAR (MAR-ADP) in the high possibility group of SDB were significantly higher than those in the low possibility group (all P<0.05); MAR-AA and MAR-ADP in the recurrent group were significantly higher than those in the non-recurrent group (all P<0.05), and the proportion of high possibility of SDB in the recurrent group was significantly higher ( P=0.008). Binary logistic regression analysis showed that homocysteine (odds ratio 1.132, 95% confidence interval 1.048-1.223; P=0.002) and having high possibility of SDB (odds ratio 6.351, 95% confidence interval 1.134-35.566; P=0.035) were the independent risk factors for stroke recurrence in patients treated with dual antiplatelet therapy. Intermediary effect analysis showed that MAR had a significant intermediary effect on the risk of stroke recurrence in patients with high probability of SDB. Conclusion:The MAR and stroke recurrence rates in the high possibility group of SDB were significantly higher than those in the low possibility group, and its stroke risk was probably mediated by platelet hyperreactivity.

Thrombotic thrombocytopenic purpura (TTP) is a rare hematological disease with typical clinical manifestations of thrombocytopenic purpura, microangiopathic hemolytic anemia, neurological symptoms, fever and kidney damage. Two patients with TTP-associated cerebral infarction complicated with microhemorrhage and their shared specific imaging findings manifestations were reported. The magnetic resonance imaging of the 2 patients showed multiple cerebral infarctions at different stages. Susceptibility-weighted imaging showed cerebral microbleeds in the infarcted area. This special imaging feature can provide important clues for early identification and diagnosis of TTP nervous system injury.