Objective To evaluate the effects of different ratios of medicine dosage for isoflurane and propofol on postoperative cognitive function of rats with mild cognitive impairment (MCI).Methods Healthy male Wistar rats,aged 16-18 months,were used in the study.MCI model was established by occlusion of bilateral common carotid arteries.One hundred and fifty rats with MCI were divided into 5 groups (n=30 each) using a random number table:sham operation group (group S),isoflurane group (group I),propofol group (group P) and different ratios of medicine dosage for isoflurane and propofol groups (IP1,2 groups).The rats inhaled 1.9％ isoflurane for 3 h in group I.Propofol 40 mg · kg-1 · h-1 was infused intravenously for 3 h in group P.The rats inhaled 1.0％ isoflurane,and propofol 20 mg · kg 1 · h-1 was infused intravenously for 3 h in group IP1.The rats inhaled 1.4％ isoflurane,and propofol 10 mg· kg-1 · h-1 was infused intravenously for 3 h in group IP2.After disappearance of eyelash reflex,open reduction and internal fixation was performed after tibial fracture was induced.On 7 days after operation,contextual fear conditioning test and Y maze test were used to assess the cognitive function,and hippocampal tissues were obtained to count the viable neurons (using Nissl's staining) and CCAAT/enhancer-binding protein homologous protein (CHOP) and caspase-12 positive neurons (by immunofluorescence) in hippocampal CA1 region.Results Compared with group S,the rate of time spent in N arm,the rate of time spent freezing,and the number of viable neurons were significantly decreased,and the number of CHOP and caspase-12 positive neurons were significantly increased in IP2,I and P groups (P＜0.05),and no significant change was found in the parameters mentioned above in group IP1 (P＞0.05).Compared with group IP1,the rate of time spent in N arm,the rate of time spent freezing,and the number of viable neurons were significantly decreased,and the number of CHOP and caspase-12 positive neurons was significantly increased in IP2,I and P groups (P＜0.05).Compared with group IP2,the rate of time spent in N arm,the rate of time spent freezing,and the number of viable neurons were significantly decreased,and the nunber of CHOP and caspase-12 positive neurons was significantly increased in I and P groups (P＜0.05).Conclusion Combination of 1.0％ isoflurane and propofol 20 mg · kg-1 · h-1 does not aggravate the postoperative cognitive dysfunction of the rats with MCI.

Objective To investigate the appropriate compatibility of appropriate compatibility of sevoflurane and propofol for patients with mild cognitive impairment (MCI) undergoing posterior lumbar interbody fusion in order to protect their cognitive function.Methods Eighty patients, 41 males, 39 females, aged 65-75 years, BMI 17-26 kg/m2, ASA physical status Ⅰ or Ⅱ, scheduled to undergo elective posterior lumbar interbody fusion, were to be scored according to Montreal cognitive assessment (MoCA), mini mental state examination (MMSE), dementia scale (CDR) and daily living ability scale (ADL) to identify patients with MCI before the surgery.They were randomly assigned to 4 groups (n=20 each) using a random number table: TCI propofol 2.0-2.5 μg/ml group (group P), TCI propofol 1.2 μg/ml+sevoflurane 0.6 MAC group (group PS1), TCI propofol 0.6 μg/ml+sevoflurane 0.9 MAC group (group PS2), 1.0-1.5 MAC sevoflurane group (group S).MoCA and MMSE were used to evaluate the cognitive function of patients 1 d before the operation (T0), after patients become wide-awake (T1), 3 d and 7 d after operation (T2 and T3).Apolipoprotein J (ApoJ) concentration related to cognitive function in blood samples, which were drawn at T0-T3 would be measured with ELISA method.Results Compared with T0, the scores of MMSE and MoCA in four groups decreased significantly (P＜0.05) at T1, the scores of MMSE and MoCA in group S decreased significantly (P＜0.05) at T2;compared with T1, the score of MMSE in the four groups increased significantly at T2, T3 (P＜0.05).The scores of MMSE at T1, T3 in group S decreased significantly compared with groups P, PS1 and PS2 (P＜0.05).The scores of MoCA at T2, T3 in group S decreased significantly compared with groups P, PS1 and PS2 (P＜0.05).Compared with T0, the concentration of plasma ApoJ in the four groups increased significantly at T1 (P＜0.05).Compared with T1, the concentration of plasma ApoJ in the four groups decreased significantly at T2 and T3 (P＜0.05).Compared with group PS1, the concentration of plasma ApoJ at T1, T3 increased significantly in groups S and group PS2 (P＜0.05).Conclusion TCI propofol 1.2 μg/ml combined with 0.6 MAC sevoflurane group is the appropriate compatibility of sevoflurane and propofol for patients with MCI undergoing posterior lumbar interbody fusion,because it has less negative influence on cognitive function and lower concentration of plasma ApoJ.

OBJECTIVETo explore the effects of principal-subordinate acupoints combination on improving myocardial ischemia, and the gene regulatory pathways for the protection of myocardial ischemia.

METHODSAccording to the random number table method, 70 SPF Wistar male rats were divided into a normal group, a model group, a LY294002 group, an insulin-like growth factors-1(IGF-1) group, a Neiguan group, an acupoint combination group and an acupoint combination + LY294002 group, 10 rats in each one. Rats in the normal group were injected with 0.9% NaCl solution, while rats in the remaining groups were treated with abdominal subcutaneous injection of isoroterenol hydrochloride to establish the rat model of myocardial ischemia. Rats in the LY294002 group and IGF-1 group were treated with injection of LY294002 solution and IGF-1 solution for 14 days. Rats in the Neiguan group were treated with electroacupuncture (EA) at "Neiguan" (PC 6) by using Han-200 EA apparatus for 10 min per treatment. Rats in the acupoint combination group were treated with EA at "Neiguan" (PC 6), "Zusanli" (ST 36) and "Guanyuan" (CV 4) by using Han-200 EA apparatus for 10 min per treatment. Rats in the acupoint combination + LY294002 group were treated with LY294002 solution for 14 days, and EA at "Neiguan" (PC 6), "Zusanli" (ST 36) and "Guanyuan" (CV 4) was given before model establishment, once a day for 21 days. EA pretreatment was given before model establishment in all acupuncture groups. The heart rate (HR) and ST segment voltage were detected before and after treatment; the myocardial pathological morphology was observed by HE staining; the expressions of P13K mRNA and Akt mRNA were tested.

RESULTSAfter modeling, HR and ST segment voltage in all intervention groups were higher than those in the normal group (all P < 0.01); after the intervention, the HR and the ST segment voltage in the acupoint combination group, IGF-1 group and IGF-1 group were improved (P < 0.01, P < 0.05), which was more significant in the acupoint combination group and Neiguan group (all P < 0.01). As for the myocardial pathological morphology, obvious myocardial ischemia was observed in the model group, and that in the LY294002 group was the most serious, and that in the acupoint combination+ LY294002 group was moderate. After intervention, the myocardial pathological damage in the IGF-1 group, Neiguan group and acupoint combination group was significant improved, which was more significant in the IGF-1 group and acupoint combination group. As for the expression of PI3K mRNA and Akt mRNA, compared with normal group, the expression of PI3K mRNA was increased in the remaining groups after modeling (P < 0.01, P < 0.05), which was more significant in the IGF-1 group and acupoint combination group (all P < 0. 01). The expression of Akt mRNA in the LY294002 group and acupoint combination + LY294002 group was reduced (P < 0. 01, P < 0.05), while that in the remaining groups was increased (P < 0.01, P < 0.05), which was more significant in the IGF-1 group and acupoint combination group (all P < 0.01).

CONCLUSIONThe principal-subordinate acupoints combination could improve heart rate and ST segment voltage in rats with chronic myocardial ischemia, reduce myocardial pathological damage, which is superior to single selection of "Neiguan" (PC 6). The PI3K/Akt signaling pathway may be involved in the regulation mechanism of principal-subordinate acupoints combination for the protection of chronic myocardial ischemia.

Acupuncture Points ; Acupuncture Therapy ; Animals ; Chronic Disease ; therapy ; Electroacupuncture ; Electrocardiography ; Heart Rate ; Humans ; Insulin-Like Growth Factor I ; metabolism ; Male ; Myocardial Ischemia ; enzymology ; pathology ; physiopathology ; therapy ; Myocardium ; pathology ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Rats ; Rats, Wistar

This study aimed to investigate the ameliorative effects of 60% ethanol elution fraction (ESMW) from Si Miao Wan on the hepatic lipid accumulation and its mechanism.TG kit, BODIPY fluorescence staining, QPCR, WB, oil red O staining, and AMPKα knockdown were used to detect the ability of ESMW to improve lipid accumulation in hepatocytes stimulated with free fatty acid.Furthermore, the effects of ESMW on the oral glucose tolerance, serum biochemical indexes, TG content in liver tissue, the expressions of mRNA and protein related to lipid metabolism in liver tissue were studied in mice fed with high fat diet to verify the mechanism of ESMW fraction on hepatic lipid accumulation.The results showed that ESMW inhibited lipid accumulation induced by free fatty acids by regulating AMPK signaling pathway, and that ESMW significantly improved the lipid metabolism of mice fed with high fat diet, with relation to AMPK signaling pathway.

Objective To estimate the value of clinical parameters (such as patients' age,longitudinal melanonychia width and location) for the differential diagnosis of malignant and benign longitudinal melanonychia as well as for the evaluation of the necessity for invasive management.Methods A retrospective study was performed on 28 cases of subungual malignant melanoma collected from 2000 to 2010 as well as on 62 cases of benign longitudinal melanonychia from 2005 to 2010.Clinical analysis was carried out to compare the differences in clinical parameters such as.patients' age,longitudinal melanonychia width and lesional location,between the malignant melanoma and benign longitudinal melanonychia cases.Logistic regression analysis and ROC method were used to determine valuable clinical parameters for the differential diagnosis of malignant and benign longitudinal melanonychia.Results Significant differences were observed in the median age at diagnosis (23.0 years vs.52.5 years,Z =5.44,P ＜ 0.01 ),age at onset (21.0 years vs.48.0 years,Z =4.70,P ＜ 0.01 ),and longitudinal melanonychia width (3.0 mm vs.15.0 mm,Z =5.69,P ＜ 0.01 ) between the patients with malignant melanoma and benign longitudinal melanonychia.The involvement of thumb and hallux was observed in 77.8％ of the subungual melanoma cases,and 48.3％ of the benign cases (x2 =6.57,P ＜ 0.05).ROC method and Logistic regression analysis indicated that the age at onset and diagnosis as well as width of longitudinal melanonychia were of diagnostic value for the differential diagnosis of malignant and benign longitudinal melanonychia.Conclusions Not all longitudinal melanonychia cases need an invasive management at the time of awareness.The age at onset and diagnosis,width of melanonychia and site of the onset appear to be valuable in the differential diagnosis of malignant and benign longitudinal melanonychia,and there is a possibility to guide clinical diagnosis and treatment by establishing a mathematical model with these parameters.

AIM: To explore the expressive role of lipoprotein-associated phospholipase A_2, high sensitive C-reactive protein and matrix metalloproteinase-9 in vulnerable atherosclerotic plaques in a rabbit model. METHODS: Forty eight New Zealand white male rabbits were randomly divided into 4 groups (12 rabbits each): control group, stable plaque group, p53 group, and p53+drug group. Rabbits in control group were fed with a regular diet and underwent sham operation. Rabbits in stable plaque group, p53 group and p53+drug group underwent balloon induced arterial wall injury and then were fed on a diet with 1% cholesterol. The animals were all fed for 3 months, then the rabbits in p53 group and p53+drug group underwent Ad5-CMV p53 transfection at 10th week. Before killed, the animals in p53+drug group underwent pharmacological triggering with Russell's viper venom (RVV) and histamine to induce the rupture of the atherosclerotic plaques. At the 1st day and before sacrifice, the serum was collected for measuring Lp-PLA_2, hs-CRP, MMP-9, HDL, LDL and VLDL. The expressions of Lp-PLA_2, hs-CRP and MMP-9 in tissues were determined by the methods of hybridization and immunohistochemistry. RESULTS: At the end of 12th week, the serum and tissue levels of Lp-PLA_2 and MMP-9 in stable plaque group, p53 group and p53+drug group were significant different from those in control group and in each group at the first day (P<0.05). The serum levels of Lp-PLA_2 and hs-CRP in p53 group and p53+drug group were significantly higher than those in control group and stable group (P<0.05). The serum levels of Lp-PLA_2, hs-CRP and MMP-9 were all significantly different between p53 group and p53+drug group (P<0.05). At the end of 12th week, pathological results showed that 4 groups were normal artery, stable plaque, vulnerable plaque and rupture plaque, respectively. The fabric cap was thicker in plaque groups than that in normal group (P<0.05). The rupture and formation of thrombus were more significant in p53+drug group than those in p53 group. The serum level of Lp-PLA_2 had negative interrelated relationship with fabric cap in plaque groups (r=-0.710, P<0.01), and hs-CRP, MMP-9 had no interrelated relationships with fabric cap in plaque groups. CONCLUSION: Base on the successful establishment of the atherosclerotic plaque animal model, serum Lp-PLA_2 shows better interrelated relationships to plaques stability. Combination with hs-CRP and MMP-9, we can exactly evaluate the nature of plaques.

Objective:To analyze clinical and pathological features of 6 cases of papular acantholytic dyskeratosis of the anogenital area.Methods:Clinical and histopathological data were collected from 6 patients with papular acantholytic dyskeratosis of the anogenital area in the Department of Dermatology, Peking University Third Hospital from January 2013 to December 2022, and retrospectively analyzed.Results:Among the 6 patients, 3 were males and 3 were females. Their ages at onset ranged from 22 to 58 years. The time from the onset to diagnosis ranged from 1 to 18 months. All patients had no family history of similar skin lesions. The 6 patients all clinically presented with multiple clustered millet-sized flesh-colored or gray-whitish papules in the perianal and genital areas, with erosions and crusts on the surface of some lesions, sometimes accompanied by pruritus. Histopathological findings of skin lesions were similar, including hyperkeratosis with focal parakeratosis, as well as acantholytic and dyskeratotic cells scattered in the epidermis. The 6 patients were treated with topical glucocorticoids or tacrolimus ointment, etc., which exhibited varying efficacy, and some skin lesions persisted with repeated attacks.Conclusions:Papular acantholytic dyskeratosis was a rare skin disease, and mostly occurred in the anogenital area. Its diagnosis should rely on both clinical manifestations and histopathological findings.

N6-methyladenosine(m6A)represents one of the most abundant modifications in eukaryotes RNA.M6A modification is catalyzed and modified by m6A methyltransferases and demethylases.The fates of m6A-modified mRNAs rely on the functions of distinct"reader"proteins that recognize them,which may affect the splicing,processing,translation or degradation of the target mRNAs.Methyltransferase-like 3(METTL3)is a catalytic core component of m6A methyltransferase compound,whose abnormal expression could lead to disordered m6A modifications and further influence the proliferation,invasion,migration and drug resistance of tumor cells.As the functions of METTL3 have been explored in depth,METTL3 inhibitors have become research hotspots.Therefore,this review focus on the different target molecules and downstream signaling pathways affected by METTL3 with the assistance of different readers in the tumorigenesis and progression of urologic tumors,and summarizes the research progress of METTL3 inhibitors,in the hope to provide insights for the prevention,diagnosis and treatment of tumors.

Objective To explore the mechanism of Lkb1 regulated epithelial regeneration in asthma by airway organoid culture.Methods Lkb1f/f(the control group,n=10)and Scgb1a1CreER;Lkb1f/fmice(the Lkb1 knockout group,n=9)were taken to establish allergic asthma models by aerosol inhalation of ovalbumin(OVA).Bronchial lavage fluid(BALF)and lung tissue were collected.The number of inflammatory cells in BALF were counted.The amount of CLCA3 positive cells was compared by immunofluorescence staining of lung tissue sections.Club cells were selected by flow cytometry for organoid culture.The average diameter of organoids and organoid formation rate were calculated.Expression levels of goblet cell marker CLCA3,cilia cell markers FOXJ1 and AMPK in Club cells were detected by RT-PCR.Results There were no significant differences in the number of macrophages,eosinophils,neutrophils and lymphocytes in BALF between the control group and the Lkb1 knockout group.The number of CLCA3 positive cells were decreased after Lkb1 knockout.Results of organoid culture showed that the average diameter of organoids derived from Club cells and organoid formation rate were decreased after the absence of Lkb1.The expression of FOXJ1 was reduced.After Lkb1 deletion,the expression of AMPKα in Club cells were decreased and the proliferation of Club cells was inhibited.Activation of AMPK,the downstream signaling pathway of Lkb1,could attenuate the effect of Lkb1 deficiency on the regeneration of Club cells.Conclusion Lkb1 promotes the proliferation of airway progenitor cells by AMPK pathway.

Objective:To compare the efficacy of 3D printing technology-assisted and conventional open reduction and internal fixation of multiple rib fracture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 61 patients with multiple rib fracture admitted to Mindong Hospital Affiliated to Fujian Medical University and Fujian Provincial Hospital from July 2018 to March 2020. There were 44 males and 17 females, with age range of 18-73 years [(45.1±12.9)years]. Unilateral lung contusion and laceration occurred in 31 patients, while bilateral in 30. There were 19 patients accompanied by hempneumothorax and 16 by flail chest. Totally, 31 patients received 3D printing technology assisted open reduction and internal fixation (3D-assisted incision group) and 30 patients received conventional open reduction and internal fixation (conventional incision group). The incision length, operation time, intraoperative blood loss, postoperative 3-day visual analogue scale (VAS), duration of pain, indwelling time of chest tube, total length of hospital stay, postoperative bone callus formation time and rate of rib bone plate loosening were comapared in two groups. The short form 36 health survey (SF-36) score (ie, physical function, physical function, physical pain, general health, energy, social function, emotional function, mental health) preoperatively, at postoperative 6-month and at the last follow-up was compareted between two groups. Complications were observed at the same time.Results:All patients were followed up for 18-38 months [(26.4±5.5)months]. In 3D-assisted incision group, the incision length was (5.9±1.3)cm, with operation time for (84.6±7.8)minutes, intraoperative blood loss for (85.5±13.9)ml, postoperative 3-day VAS for (2.5±0.5)points, duration of pain for (5.9±0.7)days, indwelling time of chest tube for (3.4±0.7)days, total length of hospital stay for (7.0±1.0)days, postoperative callus formation time for (2.6±0.7)weeks and rate of rib bone plate loosening for 3.2%(1/31). By contrast, in conventional incision group, the incision length was (10.9±2.4)cm, with operation time for (127.1±12.5)minutes, intraoperative blood loss for (183.0±30.9)ml, postoperative 3-day VAS for (6.5±0.9)points, duration of pain for (11.2±1.8)days, indwelling time of chest tube for (7.8±0.8)days, total length of hospital stay for (15.1±1.2)days, postoperative callus formation time for (4.6±0.8)weeks and rate of rib bone plate loosening for 20.0%(6/30) ( P<0.05 or 0.01). There was no significant difference in preoperative SF-36 score between the two groups ( P>0.05). At 6 months after surgery, the subscores of SF-36 in 3D-assisted incision group were higher than those in conventional incision group except for "mental health" ( P<0.05 or 0.01). At the last follow-up, all the subscores of SF-36 in 3D-assisted incision group were higher than those in conventional incision group ( P<0.05 or 0.01). There were no obvious complications such as pulmonary infection or atelectasis. Conclusions:For multiple rib fracture, 3D printing technology-assisted open reduction and internal fixation is superior to conventional open reduction and internal fixation for it can shorten incision length, operation time, indwelling time of chest tube, total length of hospital stay and postoperative bone callus formation time, reduce intraoperative blood loss, relieve postoperative pain, reduce rate of rib bone plate loosening and improve quality of life of the patients.