Objective:To evaluate the association between preoperative serum β 2-microglobulin (β 2MG) concentrations and postoperative delirium (POD) in elderly patients. Methods:The study selected patients who underwent knee or hip arthroplasty under spinal-epidural anesthesia on an elective basis at Qingdao Municipal Hospital from May 2021 to November 2022. The patients were divided into a POD group and a non-POD group based on the occurrence of POD. The study was conducted as part of the Perioperative Neurocognitive Impairment and Biomarkers Lifestyle Cohort, which was a nested case-control study. The study collected baseline data from two groups of patients and analyzed the differences between them. Logistic regression was used to identify the risk factors for POD. The stability of the regression model was tested using sensitivity analysis. The mediation model was used to examine whether cerebrospinal fluid (CSF) biomarkers mediated the relationship between β 2MG and POD. The receiver operating characteristic curve was drawn and the area under the curve was calculated to evaluate the accuracy of preoperative β 2MG concentrations and CSF biomarker concentration in predicting POD. Results:There were 57 cases in POD group and 449 cases in non-POD group. The results of logistic regression analysis showed that the increased β 2MG and CSF total tau protein (t-tau) concentrations were risk factors for POD, and the increased CSF β-amyloid 42 concentration was a protective factor for POD after adjustment for multiple confounders such as age, gender, education, Mini-Mental State Examination, history of hypertension and infusion volume ( P<0.05). The results of mediation analysis showed that the serum β 2MG′s effect on POD was partly mediated by t-tau (18.1%). The results of the receiver operating characteristic curve showed that the area under the curve of the β 2MG concentration combined with the CSF biomarker concentration was 0.742. Conclusions:Elevated preoperative serum β 2MG concentration is a risk factor for POD in elderly patients, and the relationship may be partly mediated by CSF t-tau.

ObjectiveTo preliminarily confirm the effective anti-lung cancer sites of Momordicae Semen and Epimedii Folium and study their mechanism of action. MethodOn the basis of preliminary research， the extraction method of Momordicae Semen and Epimedii Folium was optimized and the effective parts were screened under the guidance of pharmacological effects. Different ethanol elution and water elution sites of Momordicae Semen and Epimedii Folium were obtained through adsorption and elution with D101 macroporous resin. The methylthiazolyldiphenyl-tetrazolium bromide （MTT） colorimetric assay was used to detect the effects of total drug extracts and different elution sites on the proliferation of various tumor cell lines， and to screen for the optimal elution site and tumor sensitive strains. Flow cytometry was used to detect the effect of the elution sites of Momordicae Semen and Epimedii Folium on intracellular reactive oxygen species （ROS） and apoptosis in A549 cells. Western blot was used to compare the expressions of tumor protein 53 （p53）， Bcl-2-associated X protein （Bax）， cysteinyl aspartate specific proteinase-3 and 9 （Caspase-3 and Caspase-9） proteins in A549 cells. ResultThe inhibitory effect of Momordicae Semen on the proliferation of A549 cells was better than the kernel of Momordicae Semen， with 50% inhibitory concentration （IC₅₀） being （86.83±2.88） mg·L^-1 and （95.10±18.13） mg·L^-1， respectively. The effect of total extracts of Epimedii Folium on A549 anti proliferation IC₅₀ value was （4.71±0.81） mg·L^-1. The IC₅₀ values of the 40%， 60%， and 80% ethanol and anhydrous ethanol eluted macroporous resins of the total extracts of Momordicae Semen and Epimedii Folium inhibiting A549 proliferation were （45.32±4.38）、 （14.95±0.73）、 （17.07±1.76）、 （14.46±2.35）、 （51.7±2.26）、 （12.37±0.67）、 （20.29±0.93）、 and （3.43±0.91） mg·L^-1， respectively. Compared with the normal group， the 1∶1 combination of Momordicae Semen and Epimedii Folium inhibited A549 cell proliferation in a time-dependent and concentration-dependent manner. Compared with the normal group， 50 mg·L^-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased intracellular ROS expression （P<0.01）. Compared with the normal group， 12.5， 25， 50 mg·L^-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of A549 cell apoptosis （P<0.01）. Compared with the normal group， 25， 50 mg·L^-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of p53 in A549 cells （P<0.01）. Compared with the normal group， 12.5， 25， 50 mg·L^-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of Bax （P<0.01）. Compared with the normal group， 50 mg·L^-1 of the combination of Momordicae Semen and Epimedii Folium significantly reduced the expressions of Caspase-3 and Caspase-9 （P<0.01）. ConclusionThe anti-tumor effect of Momordicae Semen is better than that of the kernel of Momordicae Semen. The anti-tumor substances of Momordicae Semen and Epimedii Folium mainly concentrate in the 60% ethanol to anhydrous ethanol elution site. A549 cells are sensitive to the 1∶1 combination of Momordicae Semen and Epimedii Folium， which can effectively inhibit the cell proliferation. The mechanism may be related to increasing the generation of ROS in A549 cells， promoting their apoptosis， increasing the expressions of apoptotic proteins such as p53 and Bax， and reducing the expressions of Caspase-3 and Caspase-9.

Adrenocortical carcinoma(ACC)is the most prevalent malignant tumor of the adrenal gland and is characterized by a poor pro-gnosis in its advanced stages.Surgical resection of the tumors is typically limited to patients diagnosed in the clinical stages Ⅰ and Ⅱ,lead-ing to a high postoperative recurrence rate.The combination of mitotane(M)with etoposide(E),doxorubicin(D),and cisplatin(P)(EDP-M)is currently the only approved first-line treatment regimen for advanced ACC.However,the efficacy of chemotherapy and radiation therapy in ACC remains limited.If the EDP-M regimen proves ineffective,there are no standardized or universally accepted second-line systemic treat-ment alternatives.Research advancements in the molecular mechanisms of ACC in recent years has led to increasing investigations on tyr-osine kinase inhibitors(TKIs)targeting EGFR,VEGFR,and mTOR,as well as immune checkpoint inhibitors(ICIs).Moreover,previous studies have identified mutations in CTNBB1,TP53,KDM5A,CENP-H,and other genes that may serve as therapeutic targets or biomarkers,thereby expanding the treatment options available for ACC.ICIs are effective against diverse cancer types,including non-small cell lung cancer(NSCLC),liver cancer,renal cell cancer,and urothelial cancer.Ongoing exploration into targeted therapies and immunotherapy,especially combination treatments,holds the promise of extending the survival of patients and enhancing their quality of life.

Background Alzheimer's disease(AD)is the most common type of dementia.There has been an increasing trend in incidence rate.The drug therapy has been proven ineffective in improving the cognitive function of AD patients or delaying the disease progression,leading to perceived low adherence with treatment and low efficacy.Previous basic research shows that blue light irradiation is helpful to improve the cognitive function of AD model rats,but there is no corresponding clinical study on the improvement effect of blue light irradiation on cognitive function of AD patients.Objective To explore the efficacy of blue light irradiation in improving the cognitive function of AD patients,so as to provide references for cognitive stabilization or improvement of AD patients.Methods A sample of 155 patients who were hospitalized in Geriatric Department of Shenzhen Kangning Hospital from June 2019 to December 2023 and met the International Classification of Diseases,tenth edition(ICD-10)diagnostic criteria for AD were retrospectively selected.Among them,80 cases who received blue light irradiation combined with memantine therapy and conventional psychotherapy were the study group,and 75 cases who only received memantine therapy and conventional psychotherapy were the control group.Blue light irradiation therapy lasted for 4 weeks,5 times per week,with each session lasting for 30 min.Then Mini-Mental State Examination(MMSE)and Activity of Daily Living Scale(ADL)were administered at the baseline and after treatment.Results After treatment,study group reported an increase in MMSE total score,orientation,immediate recall,attention/calculation,delayed recall and language dimension scores(Z=-6.931,-5.773,-4.123,-3.649,-3.508,-4.733,P<0.05),and a decrease in ADL total score(Z=-7.020,P<0.05)compared to baseline data.Analysis indicated that study group scored higher on MMSE total scale,orientation,immediate recall and language dimensions(Z=-2.784,-4.621,-2.483,-3.463,P<0.05),and lower on ADL total score(Z=-3.704,P<0.05)than those of control group after treatment.Conclusion Blue light irradiation for AD patients may improve their cognitive function and activities of daily living.

Objective:To evaluate the relationship between physical activity (PA) and postoperative delirium (POD) in elderly patients undergoing knee or hip arthroplasty.Methods:The study was conducted as part of the Perioperative Neurocognitive Impairment and Biomarkers Lifestyle Cohort, which was a nested case-control study. Medical records from elderly patients undergoing elective knee or hip arthroplasty under spinal-epidural anesthesia at Qingdao Municipal Hospital from August 2022 to August 2023 were collected. The patients were divided into a POD group ( n=89) and a non-POD group ( n=221) based on the occurrence of POD. Peripheral blood samples were collected before surgery, and the cerebrospinal fluid (CSF) 2 ml was extracted after successful puncture under spinal-epidural anesthesia for determination of the concentrations of amyloid-β 42 (Aβ 42), total tau protein (t-tau), and phosphorylated tau protein (p-tau) by enzyme-linked immunosorbent assay. Logistic regression was used to analyze the influencing factors of POD, and the mediation analysis was conducted to examine the mediating role of CSF biomarker in the relationship between PA and POD. Results:Logistic regression analysis showed that the increased concentration of CSF biomarkers Aβ 42 ( OR=0.997, P=0.006), elevated ratio of Aβ 42/t-tau ( OR=0.642, P=0.003), elevated ratio of Aβ 42/p-tau ratio ( OR=0.872, P=0.001) and PA ( OR=0.374, P=0.001) were protective factors for POD, while the elevated concentrations of t-tau ( OR=1.006, P=0.001) and p-tau ( OR=1.030, P=0.011) were risk factors for POD after adjusting for multi-confounders such as hypertension, diabetes, history of drinking, years of education and Mini-Mental State Examination score. The results of the mediation analysis showed that Aβ 42 (20%), t-tau (16%), Aβ 42/t-tau (23%) and Aβ 42/p-tau (28%) played mediating roles in the relationship between PA and POD. Conclusions:PA is a protective factor for POD in elderly patients undergoing knee or hip arthroplasty and CSF biomarkers may play a mediating role in the relationship between PA and POD.

Objective:To evaluate the relationship between the preoperative sleep quality and postoperative delirium (POD) in elderly patients.Methods:Three hundred and eighty-nine patients of either sex, aged 65-90 yr, with American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, who underwent elective knee/hip arthroplasty under combined spinal-epidural anesthesia in Qingdao Municipal Hospital from May 2022 to October 2023, were selected. The Pittsburgh Sleep Quality Index scale was applied at 1 day before surgery to assess the sleep quality within 1 month before surgery. The cerebrospinal fluid (CSF) specimens 2 ml were withdrawn from the subarachnoid space before anesthesia for determination of the concentrations of biomarkers (β-amyloid), total tau protein [t-tau], and phosphorylated tau protein [p-tau]) by enzyme-linked immunosorbent assay. Patients were divided into POD group and non-POD group based on whether delirium occurred within 7 days after surgery. Logistic regression was used to identify the risk factors for POD, and the sensitivity analysis was used to test the stability of the regression models. The mediation model was used to examine whether CSF biomarkers mediated the link between sleep quality and POD. The accuracy of preoperative sleep quality and CSF biomarker concentrations in predicting the occurrence of POD was evaluated by plotting the receiver operating characteristic curve and calculating the area under the curve.Results:Two hundred and seventy-nine patients were finally included, with 33 patients in POD group and 246 patients in non-POD group. The results of logistic regression analysis showed that shorter sleep duration, use of hypnotics, daytime dysfunction within 1 month before surgery, elevated t-tau concentrations in CSF, and elevated p-tau concentrations in CSF were risk factors for POD after adjusting for multiple confounding factors such as age, sex, body mass index, years of education, Mini-Mental State Examination score, and VAS score. The results of mediating effect showed that the effect of use of hypnotics and daytime dysfunction within 1 month before surgery on POD was partially mediated by p-tau concentrations in CSF (>10%). The area under the curve of combination of daytime dysfunction, sleep duration, use of hypnotics within 1 month before surgery, and CSF biomarker concentrations in predicting POD was 0.979.Conclusions:Shortened sleep duration, use of hypnotic, and daytime dysfunction with 1 month before surgery are risk factors for POD in elderly patients, and the association between use of hypnotics and daytime dysfunction and POD is partially mediated by p-tau in CSF.

This article reported a case of hypertrophic pyloric stenosis after neonatal esophageal atresia repair. The mother of the child did not have regular prenatal care. The child was born at a gestational age of 40 weeks and 2 days of gestation, with polyhydramnios at birth, and was diagnosed with esophageal atresia and cleft palate after birth and underwent thoracoscopic esophageal-esophageal end-to-end anastomosis and esophageal-tracheal fistula ligation and was given nasogastric feeding after surgery. At four months of age, the child vomited a lot of coffee-like material after nasogastric feeding, and the ultrasonographic and upper gastroenterography findings suggested hypertrophic pyloric stenosis, which was treated surgically with good results. This case suggests that hypertrophic pyloric stenosis should be considered in children with unexplained non-bilious vomiting/feeding difficulties after esophageal atresia repair. After definitive diagnosis, laparoscopic pyloromyotomy is feasible.

BackgroundThe diagnosis of Alzheimer's disease （AD） still faces great challenges， and the advantage of electroencephalogram （EEG） diagnosis lies in its portable and non-invasive nature， so the EEG diagnosis of AD has occupied an important place in clinical research. ObjectiveTo evaluate the value of resting state EEG for AD diagnosis， and to provide references for early recognition of AD in clinical practice. MethodsClinical data of AD patients （n=59） in an Inpatient Geriatric Psychiatry Unit of Shenzhen Kangning Hospital from May 2019 to May 2022 were retrospectively analyzed， and healthy elderly individuals attending outpatient clinics at the hospital during the same period were enrolled as control group （n=54）. Eight-channel resting state EEG data were acquired， and the absolute power values in the α， β， θ and δ frequency bands and the α/θ ratio were obtained and calculated using Fast Fourier Transform （FFT）. Cognitive function assessments of patients were done by Mini-Mental State Examination （MMSE） and Montreal Cognitive Assessment （MoCA）. Spearman correlation analysis was used to examine the correlation between EEG findings and MMSE and MoCA scores of AD patienrs. Logistic regression prediction model for AD was built using currently available EEG and clinical variables， and the model performance was assessed using the receiver operating characteristic （ROC） curve and the area under curve （AUC）. ResultsThe θ-band absolute powers in the right mid-frontal （F4） and mid-lateral （F7， F8） regions were higher in AD patients than those in healthy controls， with statistically significant difference （t=-2.844， -2.825， -3.014， P<0.05 or 0.01）. The absolute powers of α/θ ratio in prefrontal （Fp1， Fp2）， mid-frontal （F3， F4） and mid-lateral （F7， F8） regions showed a notable reduction in AD patients compared with healthy controls， with statistical difference （t=2.081， 2.327， 3.423， 2.358， 3.272， 2.445， P<0.05 or 0.01）. Spearman correlation analysis denoted that MMSE score was positively correlated with the absolute powers of α-band， β-band and α/θ ratio （r=0.206， 0.288， 0.372， P<0.05 or 0.01）. MoCA score was positively correlated with β absolute powers and α/θ ratio （r=0.201， 0.315， P<0.05 or 0.01）， and negatively correlated with θ absolute power （r=-0.218， P<0.05）. ROC curve revealed an AUC of 0.882 （95% CI： 0.820~0.943）， a sensitivity of 0.966 and a specificity of 0.673 for the AD prediction model based on EEG variables， while the prediction model for AD using comprehensive variables achieved better predictive efficacy， reaching an AUC， sensitivity and specificity of 0.946 （95% CI： 0.905~0.986）， 0.948 and 0.873， respectively. ConclusionResting state EEG of AD patients is correlated with cognitive function， and are of great value in the diagnosis of AD， with θ absolute power and α/θ ratio in EEG being the most strongly correlated with AD.

Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.
Humans ; Mice ; Animals ; Depression/drug therapy* ; Gastrointestinal Microbiome ; Plant Extracts ; Ginkgo biloba

Objective:To summarize the perinatal management and prognosis of congenital chylous ascites (CCA).Methods:Clinical data of 20 infants diagnosed with CCA and treated in Guangdong Women and Children Hospital from June 2015 to November 2020 were retrospectively analyzed and described.Results:There were ten patients with isolated CCA and ten with non-isolated CCA. In isolated CCA cases, seven were cured after conservative treatment and three after postoperative conservative treatment following an ineffective surgery. Non-isolated CCA cases were complicated by intrauterine cytomegalovirus infection ( n=1), malrotation of intestine ( n=4) or bilateral chylothorax ( n=5). In addition to conservative treatment for CCA, non-isolated CCA patients also received antiviral therapy, Ladd's procedure or intrauterine/extrauterine closed thoracic drainage. Of eight patients who were firstly diagnosed with ascites before 30 gestational weeks, including four isolated and four non-isolated cases, only one underwent surgical intervention. During hospitalization, serious infections occurred in three infants with isolated CCA and two with non-isolated CCA, and were all controlled by anti-infection treatment. During a follow-up to median age of 29 months (15-82 months), none of the patients had any abnormalities except for the one with intrauterine cytomegalovirus infection who was deaf at the age of two. Conclusions:Conservative management is effective and the prognosis is generally good for most cases with isolated CCA. Treatment and prognosis of non-isolated CCA depend on its comorbidities. Gestational age at diagnosis may not be a prognostic predictor.