ObjectiveTo investigate the effects of Congrong Zonggan capsules （CRZG） on cognitive impairment in the Alzheimer's disease （AD） model of mice and its related mechanisms. MethodsSPF grade 4-week-old 5×FAD mice were divided into a model group， low-dose CRZG （0.819 g·kg^-1） and high-dose CRZG （1.638 g·kg^-1） groups， and Donepezilepezil hydrochloride group （2 mg·kg^-1）， with eight mice in each group. Eight C57 mice with the same background were set as the normal group. After one week of adaptive feeding， mice were orally administered continuously for six months. On the 5th month of drug administration， Y maze， new object recognition， and Morris water maze tests were conducted separately. After administration， mouse brain tissue was taken， and the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in brain tissue were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence （IF） was used to detect the expression of small glial cell markers Iba1， astrocyte markers GFAP， and amyloid protein 1-42 （Aβ_1-42） in the hippocampus of the brain tissue. The hematoxylin-eosin （HE） staining was used to detect pathological changes in the hippocampus of brain tissue. Western blot was used to detect the expression of nuclear factor-κB （NF-κB） p65， NOD-like receptor protein 3 （NLRP3）， cleaved Caspase-1， apoptosis-associated speck-like protein containing a CARD （ASC）， and other proteins in the brain tissue. ResultsCompared with those in the normal group， the mice in the model group had obvious cognitive impairment. The spontaneous alternation rate of the Y maze was decreased， and the discrimination index of novel object recognition was decreased significantly （P<0.01）. The escape latency in the water maze was shortened significantly （P<0.01）. The contents of IL-6 and TNF-α in brain tissue were increased. The fluorescence levels of Iba1 and Aβ_1-42 in the hippocampus were significantly increased （P<0.01）. There was a significant increase in neuronal lesions， neuronal atrophy， loose arrangement of tissue structure， and abnormal erythrocyte aggregation in the hippocampus. The protein expressions of p-NF-κB p65/NF-κB p65， cleaved Caspase-1， ASC， IL-6， and IL-1β were significantly increased （P<0.05， P<0.01）. Compared with the model group， the spontaneous alternation rate and discrimination index of the high-dose CRZG group were increased significantly （P<0.01）， and the escape latency was shortened significantly （P<0.05， P<0.01）. The content of IL-6 decreased in the brain， and that of TNF-α dropped significantly （P<0.01）. The expression of Iba1 protein and Aβ_1-42 in the hippocampus decreased significantly （P<0.05， P<0.01）. The hippocampal neurons were densely arranged， and the pyramidal nuclei were clear and centered. The abnormal aggregation of red blood cells was alleviated. The value of p-NF-κB/NF-κB proteins and the expression of ASC， cleaved Caspase-1， IL-6， and IL-1β were significantly decreased （P<0.05， P<0.01）. ConclusionCRZG can effectively improve cognitive impairment in 5×FAD mice with Alzheimer's disease， and its mechanism may be related to the regulation of the NF-κB/NLRP3 pathway to reduce the abnormal activation of microglia and inhibit neuroinflammation.

Misophonia is a psychophysiological and behavioral disorder characterized by an individual's low tolerance to specific sounds， leading to intense negative emotional experiences and physiological responses. Currently， there is no standardized and universally effective treatment for misophonia in clinical practice worldwide. This article reports the case of an 18-year-old male patient with misophonia who showed poor response to sertraline combined with exposure and response prevention therapy. Subsequently， the patient received 8 weeks of Morita therapy （once a week， 50 minutes per session）， with symptomatic improvement. By presenting this case， we explore the potential efficacy of Morita therapy in treating misophonia， aiming to provide a reference for its clinical management. ［Funded by Scientific Research Development Fund Project of Shandong Second Medical University （number， 2024FYM034）］

This paper reports a case of recurrent peritoneal dialysis-associated peritonitis caused by Salmonella, as identified through metagenomic next-generation sequencing. This patient was treated regularly with peritoneal dialysis due to stage 5 chronic kidney disease. One month ago, she was hospitalized for peritoneal dialysis-associated peritonitis. The result of bacterial culture of the dialysate was Salmonella, and she was discharged after anti-infective treatment for 3 weeks. However, on the 12th day after discharge, the patient was readmitted to the hospital due to peritonitis.Both metagenomic next-generation sequencing and bacterial culture of the fluid confirmed the presence of Salmonella. After 3 weeks of intraperitoneal and intravenous anti-infection treatment, the patient underwent metagenomic next-generation sequencing to assess pathogen eradication before discharge.

Objective:To explore the relationship between hemoglobin variability (Hb-var) and risk of all-cause death and cardiovascular death in patients with peritoneal dialysis (PD), and to provide basis for reducing the risk of death in PD patients.Methods:It was a multicenter retrospective cohort study. The clinical data of regular PD patients from Nanfang Hospital of Southern Medical University, Shunde Hospital of Southern Medical University, Foshan First People's Hospital and Ganzhou People's Hospital from July 1, 2008 to December 31, 2019 were collected. Hb-var was calculated based on hemoglobin at baseline before PD and in the first year after PD. The patients were divided into low Hb-var group, moderate Hb-var group and high Hb-var group according to the tertiles of first year Hb-var, and the differences of baseline clinical data among three groups were compared. Follow-up endpoints included death, transfer to hemodialysis, transfer to kidney transplantation, transfer to other centers, loss of follow-up, or on December 31, 2021. Cox regression analysis model was used to analyze the association of the first-year Hb-var with all-cause death and cardiovascular death. Fine-Gray competitive risk regression model was used to evaluate the impact of competitive events on mortality risk.Results:A total of 1 562 patients with PD were included in the study, aged (47.6±13.8) years old, with 821 males (52.6%) and baseline hemoglobin of 81 (69, 94) g/L. Hb-var in the first year of PD was 26.6 (16.7, 40.3) g/L. There were statistically significant differences in age, body mass index, serum albumin, hemoglobin, serum creatinine, serum calcium, serum phosphorus, intact parathyroid hormone and the proportion of renin-angiotensin system inhibitors among low Hb-var group (<20.0 g/L), moderate Hb-var group (20.0-35.5 g/L) and high Hb-var group (≥35.5 g/L, all P<0.05). The follow-up time was 33 (19, 51) months, and 208 patients (13.3%) died, among which 111 patients (53.4%) died of cardiovascular death. Multivariate Cox regression analysis showed that the higher Hb-var in the first year, the lower the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.018) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) in PD patients. Compared with low Hb-var group, the risk of all-cause death ( HR=0.56, 95% CI 0.37-0.82, P=0.003) and cardiovascular death ( HR=0.54, 95% CI 0.31-0.95, P=0.032) was lowest in the high Hb-var group. The competitive risk regression model analysis showed that Hb-var in the first year was still negatively correlated with the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.039). Conclusion:High Hb-var in the first year is associated with low risk of all-cause death and cardiovascular death in PD patients with severe anemia at baseline.

ObjectiveTo explore the efficacy and mechanism of the alcohol extract DH50 of Angelicae Pubescentis Radix in treating gouty arthritis induced by monosodium urate （MSU） crystals in vivo and in vitro. MethodFifty male SD rats were randomly assigned into five groups （n=10）： a normal group， a model group， a dexamethasone （DXMS， 0.07 mg·kg^-1） group， and low- （DH50-D， 9 mg·kg^-1） and high-dose （DH50-G， 18 mg·kg^-1） DH50 groups. The rats in the normal group and model group were administrated with the same amount of pure water. On day 5， the gouty arthritis model was established by injecting MSU into the right ankle joint of rats. The toe volume and joint inflammation index were measured 4， 8， 24， and 48 h after modeling. The pathological changes of the synovial tissue were detected by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor-alpha （TNF-α）， interleukin （IL）-1β， and IL-6 in the synovial tissue. Western blot was employed to measure the protein levels of NOD-like receptor protein 3 （NLRP3）， cysteine-aspartic protease-1 （Caspase-1）， apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain （ASC）， IL-1β， and cyclooxygenase-2 （COX-2） in the synovial tissue. Furthermore， the cell inflammation model was established with RAW264.7 cells stimulated with MSU （75 mg·L^-1）. The cell experiments were carried out with 6 groups： a normal group， a model group， a positive drug （DXMS， 100 μmol·L^-1） group， and low- （DH50-D， 25 mg·L^-1）， medium- （DH50-Z， 50 mg·L^-1）， and high-dose （DH50-G， 100 mg·L^-1） DH50 groups. Methyl thiazolyl tetrazolium （MTT） assay was employed to determine the cell viability， ELISA to determine the content of TNF-α in the supernatant of cell culture， and Western blot to determine the protein levels of NLRP3， cleaved Caspase-1， IL-1β， TNF-α， and COX-2. ResultCompared with the normal group， the rat model group showed increased toe swelling degree and joint inflammatory index （P<0.01）， serious infiltration of the synovium， elevated levels of inflammatory cytokines in the tissue homogenate （P<0.01）， and up-regulated protein levels of NLRP3， Caspase-1， ASC， IL-1β， and COX-2 （P<0.05， P<0.01）. Compared with the rat model group， low- and high-dose DH50 mitigated the toe swelling degree， decreased the joint inflammatory index， alleviated the inflammatory infiltration， lowered the levels of inflammatory cytokines in the tissue homogenate （P<0.01）， and down-regulated the expression of related proteins （P<0.05， P<0.01）. Compared with the normal group， the cell model group showed elevated level of TNF-α in the supernatant （P<0.01） and up-regulated protein levels of NLRP3， cleaved Caspase-1， IL-1β， TNF-α， and COX-2 （P<0.05）. Compared with the model group， low， medium， and high doses of DH50 lowered the level of TNF-α in the supernatant of cell culture in a dose-dependent manner and down-regulated the expression of related proteins （P<0.05， P<0.01）. ConclusionDH50 can mitigate gouty arthritis both in vitro and in vivo by inhibiting the activation of NLRP3 inflammasomes and the production of inflammatory cytokines.

ObjectiveTo investigate the effect of alcohol extract of Oroxylum indicum （MHD-80） on reducing uric acid （UA） and protecting the kidney in the hyperuricemia （HUA） model in vivo. MethodPotassium oxazine （350 mg·kg^-1） and adenine （80 mg·kg^-1） were used to construct an HUA model of mice in vivo to evaluate the mechanism related to UA reduction and the protective effect of renal function of MHD-80. Seventy male ICR mice were randomly divided into seven groups， including the normal group， model group， allopurinol group （5 mg·kg^-1）， febusotan group （5 mg·kg^-1）， and MHD-80 low-， medium-， and high-dose groups （3， 6， 12 mg·kg^-1）， with 10 in each group. Except for the normal group， the other groups were given intragastric administration of potassium oxazine and adenine for 14 consecutive days to establish the HUA model. On the 8^th to 14^th day after modeling， each group was given corresponding drugs by intragastric administration， once a day. 1 h after the last administration， blood was collected from the eyeballs， and kidney and liver tissues of mice were collected. Serum levels of UA， urea nitrogen （BUN）， and creatinine （Cr） and liver activity of xanthine oxidase （XOD） were determined by enzyme colorimetry. Serum contents of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） were determined by enzyme-linked immunosorbent assay （ELISA）. Hematoxilin-eosin （HE） staining was used to observe the pathological changes in kidney tissues. The protein expression levels of ATP-binding box transporter G2 （ABCG2） and glucose-facilitating transporter 9 （GLUT9） in kidney tissues were detected by Western blot. ResultIn vivo experiment shows that compared with the normal group， the serum levels of UA， Cr， BUN， inflammatory factors TNF-α， IL-1β， and liver XOD activity in the serum of mice in the model group were significantly increased （P<0.05， P<0.01）， and the expression of GLUT9 in kidney tissues was significantly up-regulated （P<0.05）. ABCG2 protein expression was significantly down-regulated （P<0.05）， and renal injury was obvious. Compared with the model group， the levels of UA， BUN， Cr， TNF-α， IL-1β， and liver XOD activity in the serum of mice in the high-dose group of MHD-80 were decreased to different degrees （P<0.05， P<0.01）， GLUT9 protein expression was significantly down-regulated （P<0.01）， ABCG2 protein expression was significantly up-regulated （P<0.05） in the high-dose group of MHD-80， and the degree of renal injury was reduced. ConclusionMHD-80 has certain uric acid reduction， anti-inflammatory， and anti-renal injury effects， which are related to inhibiting XOD activity and regulating the expression of ABCG2 and GLUT9 uric acid transporter.

Objective:To compare the survival rate of secondary hyperparathyroidism (SHPT) patients with different dialysis modalities after parathyroidectomy (PTX), and analyze the influencing factors of survival prognosis.Methods:Clinical data of dialysis patients diagnosed with SHPT and treated with PTX in the First People′s Hospital of Foshan from April 2014 to May 2019 were retrospectively collected and analyzed. The patients were divided into hemodialysis (HD) group and peritoneal dialysis (PD) group according to preoperative dialysis modalities, and the differences in baseline clinical data and cardiac ultrasound results were compared between the two groups. Kaplan-Meier survival analysis was used to compare the difference in cumulative survival rate between the two groups. Multivariate Cox regression model was used to analyze the influencing factors of all-cause death. Receiver operating characteristic curve (ROC curve) was used to predict the risk of all-cause death.Results:A total of 99 patients were enrolled in this study, and 94 patients completed follow-up, including 23 patients who died. Compared with PD group ( n=45), HD group ( n=54) had higher dialysis age, blood pressure, intact parathyroid hormone, alkaline phosphatase, total heart valve calcification rate, mitral valve calcification proportion, interventricular septal thickness (IVST) and left ventricular mass index (all P<0.05). The median follow-up time was 46.00(32.75, 60.25) months. Kaplan-Meier survival analysis showed that there was no significant difference in cumulative survival rate between HD group and PD group (Log-rank test χ2=0.414, P=0.520). Multivariate Cox regression analysis showed that increasing age ( HR=1.066, 95% CI 1.017-1.118, P=0.008), systolic blood pressure>140 mmHg ( HR=2.601, 95% CI 1.002-6.752, P=0.049) and increasing IVST ( HR=1.269, 95% CI 1.036-1.554, P=0.021) were independent influencing factors for all-cause death in dialysis patients after PTX. ROC curve analysis results showed that the cut-off values of age, dialysis age and IVST for predicting all-cause death after PTX were 51.5 years old ( AUC=0.673, 95% CI 0.545-0.802, P=0.013) and 75.0 months ( AUC=0.654, 95% CI 0.528-0.780, P=0.027) and 13.5 mm ( AUC=0.680, 95% CI 0.557-0.803, P=0.010) respectively. The area under the ROC curve for age, dialysis age, IVST, left ventricular hypertrophy in combination with systolic blood pressure>140 mmHg in the prediction of all-cause death after PTX was 0.776(95% CI 0.677-0.875, P<0.001). Conclusions:There is no significant difference in cumulative survival rate between HD and PD patients with SHPT after PTX. Increasing age, systolic blood pressure>140 mmHg and increasing IVST are independent risk factors for all-cause death in dialysis patients with SHPT after PTX.

Objective:To investigate the clinical features, diagnosis, and treatment of the central nervous system (CNS) toxicity caused by bortezomib.Methods:This study reports five new cases of CNS toxicity caused by bortezomib to elucidate its characteristics along with a review of the literature.Results:CNS toxicity caused by bortezomib presents in three clinical forms: syndrome of inappropriate antidiuresis (SIAD) , posterior reversible encephalopathy syndrome (PRES) , and central fever, which is the most common clinical manifestation. Four of our five patients developed central fever after the administration of bortezomib, manifested as persistent high fever, anhidrosis, and absence of infective foci; the symptom could be improved by discontinuance of bortezomib. Of these patients, three concurrently presented with refractory hyponatremia and one was clearly diagnosed with SIAD. The bortezomib could have caused damages to the hypothalamus and induced both central fever and SIAD. In addition, one patient was diagnosed with PRES due to disturbance of consciousness and epilepsy after taking bortezomib. After discontinuation of bortezomib, the symptoms disappeared and did not recur. We also found that thrombocytopenia may be related to the severity of the CNS toxicity of bortezomib.Conclusion:Cases of CNS toxicity of bortezomib are extremely rare and present as SIAD, PRES and central fever. Early detection and treatment of bortezomib are very important to prevent irreversible neurological complications.

Objective:To observe the changes of abdominal aortic calcification and biochemical indicators after parathyroidectomy (PTX) in the maintenance hemodialysis (MHD) patients with secondary hyperparathyroidism (SHPT).Methods:The MHD patients with SHPT who were followed up for 2 years were analyzed retrospectively and divided into PTX surgery group ( n=26) and non-surgery group ( n=18) according to whether they underwent PTX, and then the abdominal aortic calcification score (AACS), intact parathyroid hormone (iPTH), blood calcium and phosphorus after 2 years were observed in the two groups. The PTX surgery group was divided into advanced group and non-advanced group according to whether abdominal aortic calcification had progressed or not 2 years after the operation. Indicators such as age, dialysis age, iPTH, blood calcium, blood phosphorus, calcium and phosphorus product were compared between the two groups to analyze the possible factors related to the development of abdominal aortic calcification. Results:A total of 44 patients meeting the inclusion criteria were included, with 26 in the PTX surgery group and 18 in the non-surgery group. The baseline data of the PTX surgery group and the non-surgery group showed statistical difference in the age of dialysis ( P<0.05), but no statistical differences in gender, age and history of hypertension. Compared with preoperative indicators, postoperative iPTH, blood calcium and phosphorus significantly reduced (all P<0.05), and there was no significant difference in AACS. There were 8 cases (30.77%) of accelerating progress of calcification, 8 cases (30.77%) of improvement in calcification, 10 cases (38.46%) of calcification stability. After 2 years, iPTH value of non-advanced group was significantly lower than advanced group [(20.62±6.44) ng/L vs (132.72±76.83) ng/L], while the preoperative AACS progress was higher in non-advanced group [(13.11±2.71) vs (2.00±1.41)] (all P<0.05). In non-surgery group, AACS was significantly higher after 2 years [(10.44±1.65) vs (8.05±1.26)], blood phosphorus and the product of blood calcium and phosphorus significantly decreased (all P<0.05) , and the levels of iPTH and blood calcium did not significantly change. Pearson correlation analysis showed that the decreased value between preoperative AACS and 2-year postoperative AACS was positively correlated with the decreased value of iPTH ( r=0.534, P=0.012), blood calcium ( r=0.643, P=0.004), blood phosphorus ( r=0.897, P<0.001) and calcium-phosphorus product ( r=0.568, P=0.021) , and negatively correlated with preoperative AACS ( r=-0.647, P=0.014). Conclusions:Small sample data shows that PTX can correct parathyroid hormone, calcium and phosphorus for long term, and prevent abdominal aortic calcification progression, even reverse vascular calcification. Whether abdominal aortic calcification improves or not may be associated with the decrease of iPTH, calcium, phosphorus and the product of blood calcium and phosphorus.

Objective To investigate the relationship between serum uric acid level and renal function decline by retrospective cohort study.Methods Through the physical examination system of the First People's Hospital of Foshan,the physical examination data from 2015 to 2018 of a public institution in Foshan city were obtained.The gender,age,blood cell analysis,liver function,serum creatinine,uric acid,fasting blood glucose were obtained.The change of eGFR (△eGFR=eGFR2018-eGFR2015) was analyzed.Results A total of 2505 subjects were followed up for four years.The subjects were divided into △eGFR ≥0 group and △eGFR ＜ 0 group.There were 845 subjects in △eGFR ≥0 group,and 1660 subjects in △eGFR ＜ 0 group.Compared with that in △eGFR ＜ 0 group,the base-level of uric acid in △eGFR ≥ 0 group was higher [(349.48±87.62) μmol/L vs (325.72±82.58) μmol/L,t=6.669,P ＜ 0.001],but the rate of uric acid decline was greater [-15.00(-53.50,17.00) μmol/L vs 15.50(-18.00,49.00) μmol/L,Z=-13.470,P ＜ 0.001].According to the levels of uric acid in 2015 and 2018,then the subjects were divided into four groups,normal to normal group (N-N,1551 cases),normal change into high uric acid group (N-H,299 cases),high uric acid drop to normal group (H-N,238 cases),and high to high uric acid group (H-H,417 cases).The △eGFR was-1.58(-4.17,1.01) ml · min-1 · (1.73 m2) 1 in N-N group,and-3.60(-7.24,-0.98) ml · min-1 · (1.73 m2)-1 in N-H group,-0.20(-3.14,3.27) ml· min-1· (1.73 m2)-1 in H-N group,-0.96(-4.07,1.93) ml· min-1· (1.73 m2)-1 in H-H group,respectively.The △eGFR decreased most significantly in N-H group than the other three groups (x2=103.130,P ＜ 0.001).Multivariate logistic regression analysis showed that elevated uric acid was an independent risk factor for eGFR decline (OR=1.739,95％CI 1.587-1.906,P ＜ 0.001),while elevated indirect bilirubin (OR=0.968,95％CI 0.943-0.993,P=0.013),elevated red blood cells (OR=0.815,95％ CI 0.680-0.976,P=0.026) were independent protective factors for eGFR decline.Conclusion Elevated uric acid is an independent risk factor for the decline of renal function.Good control of hyperuricemia is beneficial to the protection of renal function.