OBJECTIVE: To observe the effects of "olfactory three needles" on cognition, learning and memory abilities, as well as hippocampal microglia (MG) phagocytic activity in vascular dementia (VD) rats, and explore the mechanisms of acupuncture in regulating MG activation and improving remyelination, so as to ameliorate VD. METHODS: Among 38 SD rats meeting experimental requirements, 9 rats were randomly assigned to a sham-operation group, and the remaining rats underwent permanent bilateral common carotid artery ligation to establish VD model. Eighteen successfully modeled rats were randomly divided into a model group and an electroacupuncture (EA) group, with 9 rats in each one. In the EA group, EA was performed at "olfactory three needles" ("Yintang" [GV24⁺] and bilateral "Yingxiang" [LI20]), at disperse-dense wave, the frequency of 2 Hz/15 Hz and the current intensity of 1 mA, for 15 min per intervention, once daily. One course was composed of 7 days, and 2 courses were required, with the interval of 2 days. The novel object recognition test was employed to assess the cognition of rats, and the Morris water maze was adopted to observe learning and memory abilities. Luxol fast blue (LFB) staining was performed to evaluate myelin sheath loss in the hippocampus, the Western blot was used to detect the protein expression of triggering receptor expressed on myeloid cells-2 (TREM2) and proteolipid protein (PLP) in the hippocampus; and the immunofluorescence staining was used to detect the positive expression of PLP, sex determining region Y-box 10 (SOX10), ionized calcium binding adaptor molecule 1 (Iba1)⁺ TREM2⁺ and Iba1⁺ lysosome-associated membrane protein 1 (LAMP1)⁺ in the hippocampus. RESULTS: Compared with the sham-operation group, the rats in the model group exhibited the prolonged escape latency on day 3 and 4 (P<0.05, P<0.01), the increase of the total distance traveling (P<0.01) and the decrease of the recognition index (RI) and platform crossing frequency (P<0.01). Compared with the model group, the rats in the EA group showed the shortened escape latency on day 3 and 4 (P<0.05), the decrease of total distance traveling (P<0.01) and the increase of RI and platform crossing frequency (P<0.05, P<0.01). When compared with the sham-operation group, the rats of the model group presented uneven staining, sparse arrangement of myelin sheath fibers, unclear contours, and prominent vacuole-like changes in the hippocampal CA1 region. When compared with the model group, the EA group showed more dense staining, the increase of myelin sheath fibers with more orderly alignment, and fewer vacuolar changes in the hippocampal CA1 region. Compared with the sham-operation group, the model group exhibited the increase of TREM2 protein expression and the decrease of PLP protein expression in the hippocampus (P<0.01), whereas the EA group showed the up-regulation of TREM2 and PLP protein expression when compared with the model group (P<0.01, P<0.05). The positive expression of the hippocampal PLP, SOX10, and Iba1⁺LAMP1⁺ in the model group was reduced in comparison with the sham-operation group (P<0.05, P<0.01), and the positive expression of Iba1⁺ TREM2⁺ was elevated (P<0.05). In the EA group, the positive expression of PLP, SOX10, Iba1⁺TREM2⁺, and Iba1⁺ LAMP1⁺ was higher compared with that in the model group (P<0.05, P<0.01). CONCLUSION "Olfactory three needles" can improve the learning and memory, and cognitive functions of VD rats, and its mechanism may be associated with the up-regulation of TREM2 and LAMP1 to adjust MG phagocytic activity and intracellular degradation, and promote remyelination.
Animals ; Dementia, Vascular/metabolism* ; Rats ; Rats, Sprague-Dawley ; Microglia/metabolism* ; Male ; Acupuncture Therapy/instrumentation* ; Acupuncture Points ; Humans ; Remyelination ; Memory ; Hippocampus/cytology* ; Cognition ; Electroacupuncture ; Needles

OBJECTIVES: To explore the correlation of hypertension with postoperative cognitive dysfunction and its possible mechanism. METHODS: Twelve-week-old spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were both randomized into control group and surgical group (n=8). In the latter group, the rats received carotid artery exposure surgery under sevoflurane anesthesia to establish models of postoperative learning and memory impairment. Postoperative cognitive function changes of the rats were evaluated using behavioral tests. The hippocampus of the rats were collected for determining ATP level and mitochondrial membrane potential (MMP) and for detecting expressions of UCP2 and astrocyte markers (GFAP and NOX4) using Western blotting and immunofluorescence staining. Serum levels of ROS, IL-6, IL-1β and TNF‑α were detected using ELISA. Nissl staining was used to examine hippocampal neuronal loss in the CA1 region. RESULTS: The SHRs exhibited exacerbated learning and memory deficits following the surgery as shown by significantly reduced performance in novel object recognition tests and context-related and tone-related fear conditioning experiments. Compared with WKY rats, the SHRs had significantly decreased mitochondrial UCP2 expression and MMP in the hippocampus, increased hippocampal ATP level, and markedly increased serum levels of ROS and inflammatory factors, showing also increased activation of hippocampal astrocytes and microglia and reduced number of neurons positive for Nissl staining. CONCLUSIONS Hypertension can exacerbate major postoperative learning and memory impairment in rats possibly as a result of UCP2-mediated mitochondrial dysfunction and oxidative stress damage, which further leads to astrocyte overactivation and neuronal damage.
Animals ; Rats, Inbred SHR ; Rats ; Uncoupling Protein 2 ; Rats, Inbred WKY ; Hypertension/physiopathology* ; Hippocampus/metabolism* ; Mitochondria/metabolism* ; Down-Regulation ; Male ; Memory Disorders/etiology* ; Mitochondrial Proteins/metabolism*

Objective To analyze the risk factors of poor prognosis in patients with extended-spectrum β-lactamase producing enterobacterales(ESBL-E)bloodstream infection,and establish a nomogram prediction model to provide help for clinical diagnosis and treatment.Methods A total of 235 patients with ESBL-E bloodstream infection were collected from the First People's Hospital of Jiande City.According to their prognosis,the patients were divided into survival group(n=211)and death group(n=224).The clinical data of the patients were collected,and the independent risk factors of poor prognosis were screened by multivariate Logistic regression analysis.The nomogram was established and verified.Results The mortality of ESBL-E bloodstream infection patients with shock,respiratory failure,diabetes and leukemia,ICU admission,hypoproteinemia,increased or decreased white blood cells,and thrombocytopenia was higher(P＜0.05).Multivariate Logistic regression analysis showed that combined shock,respiratory failure and leukemia were independent risk factors for death from ESBL-E bloodstream infection.Conclusion The nomogram prediction model of adverse prognostic risk factors in patients with ESBL-E bloodstream infection can provide help for clinicians to judge the poor prognosis in the early stage,and it is of reference significance to take early intervention measures to reduce the mortality of patients.

Objective To observe the value of spectral CT multi-parameter imaging for preoperative predicting lymph node metastasis(LNM)of gastric cancer.Methods Totally 136 patients with gastric adenocarcinoma were retrospectively enrolled.The patients were further divided into LNM group(n=74)and non-LNM group(n=62)according to postoperative pathological findings of lymph nodes status.Clinical data,conventional CT findings and spectral CT parameters were compared between groups.Factors being significant different between groups were included in multivariate logistic regression analysis to screen independent predictors of gastric cancer LNM.Clinical+conventional CT model(model 1),spectrum CT model(model 2)and combined model(model 3)were constructed based on the above independent predictors,respectively.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of each model for preoperative predicting LNM of gastric cancer.Results CT-N stage,CT-T stage,70,100 and 140 keV CT valuestumor at arterial phase(AP),arterial enhancement fraction(AEF)and normalized iodine concentration at venous phase(NICVP)were all independent predictors of gastric cancer LNM(all P＜0.05).AUC of model 3 was 0.846,higher than that of model 1 and model 2(AUC=0.767,0.774,Z=-0.368,-2.373,both P＜0.05)for preoperative predicting LNM of gastric cancer,while the latter two were not significantly different(Z=-0.152,P=0.879).Conclusion Spectral CT multi-parameter imaging could effectively predict LNM of gastric cancer preoperatively.

Objective To investigate the value of pulse oxygen perfusion index(PI)and blood lactic acid(BLA)concentration in early prediction of retinopathy of prematurity(ROP).Methods A retrospective case-control study was conducted on 128 preterm infants who met the inclusion criteria and were admitted to the neonatal intensive care unit of our hospital from September 2018 to December 2022.Among them,46 patients with ROP were in the ROP group,and 82 pa-tients without ROP were in the non-ROP group.Basic data of these preterm infants were recorded after admission.PI val-ues were continuously monitored with the Masimo Radical-7(USA)SpO2 blood oxygen saturation detector,and BLA con-centrations were detected with the ABL90FLEX blood gas analyzer.The receiver operating characteristic(ROC)curve and area under curve(AUC)were used to evaluate the value of PI and BLA concentration in early prediction of ROP.Results There were no significant differences in gestational age,birth weight,sex,and delivery mode between the two groups(all P＞0.05).The PI values after birth were significantly different between the two groups(Fgroup=15.393,Pgroup＜0.001).The PI values of preterm infants in the ROP group decreased significantly at 1 h,12 h and 24 h after birth and slightly at 48 h to 96 h after birth compared with the non-ROP group.The PI values of preterm infants in the two groups sta-bilized at 96 h after birth.The PI values of preterm infants in the ROP group were lower than those in the non-ROP group at all time points within 96 h after birth(all P＜0.05).The PI values showed interaction effects between the two groups at different time points(Finteraction=5.061,Pinteraction＜0.001).There was a significant difference in BLA concentration between the two groups after birth(Fgroup=91.158,Pgroup＜0.001).In the ROP group,the BLA concentration increased significantly at 1 h after birth and slightly at 12 h and 24 h after birth compared with the non-ROP group.The BLA concentration in the ROP group was higher than that in the non-ROP group at all time points after birth(all P＜0.05).The BLA concentration showed no interaction effects between the two groups at different time points(Finteraction=0.567,Pinteraction＞0.05).The AUC of PI values at 1 h,12 h and 24 h after birth and BLA concentration at 1 h after birth for predicting ROP was 0.77,0.82,0.83,and 0.82,respectively.The AUC of combined PI values at 1 h,12 h and 24 h after birth and BLA concentration at 1 h after birth for predicting ROP was 0.94,higher than the predictive value of a single indicator.Conclusion PI and BLA concentration have good clinical value for early prediction of ROP.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

OBJECTIVE：To establish a method for the content determination of potential genotoxic impurity maleic hydrazide in azintamide raw material. METHODS ：HPLC-FLD method was adopted. The determination was performed on Thermo Syncronis C18 column with mobile phase consisted of 0.2 mol/L acetic acid-methanol （gradient elution ）. The column temperature was set at 30 ℃，the excitation wavelength was 315 nm and emission wavelength was 389 nm. The flow rate was 1 mL/min，and the sample size was 20 μL. RESULTS：The blank solvent and azintamide did not interfere with the determination of maleic hydrazide. The linear range of maleic hydrazide was 19.5-300 ng/mL（r＝0.999 9）. The limit of detection was 4.5 ng/mL and the limit of quantification was 19.5 ng/mL. The recovery ranged from 98.79％ to 103.76％（RSDs were lower than 3.00％，n＝9）. RSDs of precision and stability （24 h）tests were no more than 5.63％，and those of durability tests were less than 2.00％（n＝6）. Maleic hydrazide was not detected in 3 batches of azinamide raw material. CONCLUSIONS ：The method is specific ，sensitive and accurate. It can be used for the trace determination of maleic hydrazide in azintamide or other matrix.

Objective:To evaluate the safety and efficacy of endovascular interventional treatment of the intracranial vertebrobasilar trunk large aneurysms (VBTLAs) compared with conservative treatment.Methods:This is a prospective multi-center cohort study. From October 2012 to October 2018, a total of 69 patients with intracranial vertebrobasilar trunk large aneurysm (diameter>10 mm) from Henan Province People's Hospital and People's Liberation Army Rocket Medical Center were included in this study. Patients themselves chose either endovascular interventional therapy (interventional group) or conservative treatment (conservative group) after discussion with their doctors. The χ 2 test was used to compare the incidence of deaths, stroke, and all other serious adverse events including other site bleeding, myocardial infarction and others between the two groups. Results:A total of 69 patients were enrolled, of whom 51 patients were enrolled in interventional group, 18 patients underwent endovascular reconstructive therapy, 11 patients underwent deconstructive therapy, and 4 patients underwent conjunction interventional treatments. Eighteen patients were enrolled in conservative group, of whom 11 cases received simple risk factor control, 7 cases received antiplatelet and risk factors control. The proportions of hypertensive patients 94.4% (17/18) and giant aneurysms 50.0% (9/18) in the conservative group were higher than those in the surgery group 64.7% (33/51, χ 2=4.500, P=0.034), 19.6% (10/51, χ 2=4.730, P= 0.030).The incidence of all serious adverse events associated with protocol was 15.7% (8/51) in the interventional group and 44.4% (8/18) in the conservative group [risk ratio (RR) =0.353, 95% confidence intervals (CI): 0.156-0.801], and the difference was significant (χ 2=4.668, P=0.031). The incidence of fatal events associated with protocol was 2.0% (1/51) in the interventional group and 38.9% (7/18) in the conservative group (RR=0.050, 95%CI: 0.007-0.382), and the difference was significant (χ 2=14.281, P<0.001). The incidence of hemorrhage events associated with protocol was 2.0% (1/51) in the interventional group and 22.2% (4/18) in the conservative group (RR=0.088, 95%CI: 0.011-0.738), and the difference was significant (χ 2 =5.391, P=0.020). Follow-up imaging showed that the occlusion rate of aneurysms in 44 patients in the interventional group was 56.8% (25/44) after a median follow-up of 6 months. Imaging follow-up was obtained in 9 patients, whose occlusion rate of aneurysms was 0 and the median follow-up time was 12 months, in the conservative group. The difference was significant(χ 2 =7.534, P=0.006). Conclusion:Compared with conservative treatment, endovascular intervention of the intracranial VBTLAs has lower incidences of serious adverse events and death events.

Objective: To investigate the aggravation of pancreatic tissue injury in rats with acute hypertriglyceridemic pancreatitis and the possible role of NADPH oxidase (NOX). Methods: Thirty SPF rats were randomly (random number)divided into five groups: N group, H group, NLAP group, HLAP group and HAPO group. AMY, TG, TC and FFA levels were detected. The pathological changes of pancreas were observed under light microscope and the ultrastructural changes of pancreatic acinar cells were observed by TEM. Serum levels of MDA, SOD, IL-1β, TNF-α and LDH were detected. The expression of NOX4, p-Akt and p-GSK3β in pancreas was detected by immunofluorescence, and the expression of NF-κB and TNF-α in pancreas was detected by immunohistochemistry. Results: Intraperitoneal injection of P-407 could significantly increase the levels of serum TG, TC and FFA in rats. After acute pancreatitis induced by L-Arg, the levels of serum AMY in the NLAP and HLAP groups were significantly increased, while Apocynin could significantly decrease the level of serum AMY. Compared with the NLAP group, the pathological injury of pancreatic tissue in the HLAP group was more serious, the level of inflammatory mediators was significantly increased, and the cell necrosis was more serious. After inhibiting NOX, the activation of Akt/GSK3β pathway was regulated and the pancreatic injury was improved. Conclusion In HTGP, NOX aggravates pancreatic injury by regulating the activation of Akt/GSK3 β pathway. Inhibition of NOX expression can play a protective role in pancreas injury of HTGP..

Objective To explore the protective mechanism of glycogen synthase kinase-3β(GSK-3β) inhibitor TDZD-8 on acute necrotizing pancreatitis (ANP) associated kidney injury in rats. Methods SPF male Wistar rats were randomly divided into four groups (n = 20): sham operation group (Sham group), ANP model group, TDZD-8 intervention group and TDZD-8 control group. The rat ANP model was prepared by retrograde injection of 5% sodium taurocholate into the bile duct; the same volume of normal saline was injected into the pancreatic duct of the Sham group. The TDZD-8 intervention group and the TDZD-8 control group were injected with GSK-3β inhibitor TDZD-8 (1 mL/kg) via the femoral vein 30 minutes before the model or sham operation; the ANP model group and the Sham group were injected equal volume of 10% dimethyl sulfoxide (DMSO). Rats in each group were sacrificed at 12 hours after operation to measure the serum amylase (AMY), blood lipase (LIPA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels and to observe the pathological changes of pancreatic tissues and kidney tissues. Ultrastructural change of renal cells was analyzed by transmission electron microscopy. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were evaluated by enzyme linked immunosorbent assay (ELISA). The activation of nuclear factor-κB p65 (NF-κB p65) was evaluated by immunohistochemistry assay. The protein expressions of GSK-3β, phospho-GSK-3β (Ser 9), tumor necrosis factor -α (TNF-α), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and interleukin-10 (IL-10) in the kidney were determined by Western Blot. Results Compared with the Sham group, the serum and inflammatory factors levels of the ANP model group were significantly increased, the pathological damage of the pancreas and kidney tissues were severe, the histopathological score was significantly increased, the expression of NF-κB p65 was enhanced in the nucleus of the kidney tissue, and the expressions of GSK-3β, TNF-α, ICAM-1 and iNOS were significantly enhanced, and the expressions of p-GSK-3β(Ser 9) and IL-10 were significantly attenuated. Compared with the ANP model group, TDZD-8 pretreatment significantly reduced serum and inflammatory factor levels in the ANP model group [AMY (kU/L): 5.60±0.30 vs. 10.07±0.34, LIPA (U/L): 1 111.0±110.8 vs. 2 375.0±51.1, SCr (μmol/L): 47.38±1.48 vs. 72.50±2.43, BUN (mmol/L): 17.6±1.0 vs. 26.0±1.0, IL-1β (ng/L):195.90±5.50 vs. 332.40±38.29, IL-6 (ng/L): 246.10±26.74 vs. 385.30±32.19, all P < 0.01]; pathological damage of pancreas and kidney tissue (histopathological score: 7.1±0.4 vs. 12.1±0.3, 301.2±7.5 vs. 433.5±13.8, both P < 0.01) and ultrastructural damage of renal cells were alleviated; the expression of NF-κB p65 in the nucleus was significantly decreased; the expression of p-GSK-3β(Ser 9) was significantly increased, and blocking GSK-3β activity could inhibit the expressions of TNF-α, ICAM-1, iNOS and increase the expression of IL-10, while the expression of GSK-3β in renal tissues was not statistically significant. There were no significant differences between the TDZD-8 control group and the Sham group. Conclusions Blockade of GSK-3βactivity by TDZD-8 exerts the protective effect against kidney injury by inhibiting the inflammation signaling pathway in ANP. It can alleviate histopathological and ultrastructural changes in kidney injury, which protection mechanism is mediated by NF-κB and its related inflammatory mediators.