Objective:To study the neuroprotective effect of nobiletin on the symptoms of postoperative cognitive impairment (POCD) induced by sevoflurane inhalation.Methods:Twenty-four aged SD rats (12 female mice and 12 male mice) were divided into three groups randomly: control group ( n=8), surgery group ( n=8) and surgery + nobiletin group ( n=8), with 4 females and 4 males in each group.The rats in surgery group and surgery+ nobiletin group were given normal saline(0.1 ml/10 g, once a day) and nobiletin(100 mg/kg, once a day) intragastrically for 6 weeks.Then the rats were anesthetized by sevoflurane and treated by abdominal exploration surgery, and then continued gavage for 1 week.The rats in control group were given normal saline(0.1 ml/10 g, once a day) intragastrically for 7 weeks without anesthesia or surgery.Sevoflurane inhalation anesthesia and abbreviated laparotomy were not done for control group.Morris water maze and open field experiment were used to measure the memory and cognitive ability and the independent exploration ability respectively.The changes of α-band electroencephalogram (EEG) were recorded by multi-channel physiological signal acquisition and processing system.The concentration of S100β, a marker of neurological impairment was detected by ELISA.Western blot was used to detect the expression level of IBA-1 in microglia.SPSS 20.0 software was used to analyze the data. Results:There were no significant differences in Morris water maze, positioning cruise test and open field test among the groups before operation (all P>0.05). The differences were statistically significant among the groups 7 days after operation (all P<0.05). Compared with the control group (the escape latency, path length and cross platform times were ((20.37±1.11)s, (552.37±14.19)cm, (6.75±0.43)times respectively), the escape latency ((40.87±2.03)s) and path length ((1 258.62±19.53)cm) of rats in surgery group were significantly longer (both P<0.01), and the cross platform times ((2.12±0.33)times) significantly reduced ( P<0.01). The differences between surgery + nobiletin group ((22.37±1.11)s, (584.50±10.90)cm, (6.62±0.48)times) and control group were not significant (all P>0.05). The open field experiment showed that the movement distance, the crossed square number, and activity times in surgery group ((1.78±0.55) m, (4.75±0.50), (14.87±0.33) times) decreased significantly compared with those in control group ((3.73±0.07) m, (11.10±0.78), (51.12±0.78) times, all P<0.01). No significant difference was found between surgery + nobiletin group ((3.76±0.07)m, (10.75±0.66), (50.75±0.43)times) and control group(all P>0.05). Before anesthesia, there was no significant difference in the power ratio of α-band among the three groups ( P>0.05), but the differences during anesthesia and operation were significant ( F=72.58, 101.50, P<0.01). During anesthesia and operation, the power ratio of α-band in anesthesia and in surgery group (2.51±0.04, 2.14±0.03) were significantly lower (both P<0.01) than those in control group (3.49±0.03, 3.49±0.03), while there was no obvious changes (both P>0.05) in the surgery + nobiletin group (3.50±0.04, 3.51±0.04). There were significant differences in Bcl-2 protein expression and caspase 3/7 protein activity among the three groups ( F=5.21, 7.84, P<0.01). Compared with control group (1.00±0.02, 1 557.46±3.63), Bcl-2 of rats in the surgery group(0.40±0.05) were significantly lower and Caspase3/7 expression of surgery group (3 689.58±10.46) was significantly higher (both P<0.01), while the rats in the surgery + nobiletin group had no significant difference in both Bcl-2 level (1.03±0.06) and caspase 3/7 activities (1 805.28±6.17, both P>0.05). The difference of S100 β protein expression was significant among the three groups ( F=490.80, P<0.01). Compared with the control group ((0.18±0.01)μg/L), the concentration of S100β protein in the surgery group ((2.13±0.02)μg/L) decreased ( P<0.01), while there was no significant difference in the surgery + nobiletin group ((0.16±0.01) μg/L, P>0.05). The expression levels of IBA-1 protein ( F=10.83) and TNF-α, IL-1, IL-1β and IL-6 ( F=996.20, 221.40, 73.02, 174.13) were significantly different among the three groups (all P<0.01). The expression level of the neuroglial marker IBA-1 in the surgery group(1.36±0.02) was significantly higher than that in the control group (1.00±0.01, P<0.01), while the surgery + nobiletin group (1.03±0.01) had no significant different compared with control group ( P>0.05). The levels of inflammatory factors, including TNF-α, IL-1, IL-1β and IL-6, in the brain of rats treated with nobiletin ((49.06±3.63)pg/mg, (2.09±0.43)pg/mg, (16.27±0.80)pg/mg, (2.11±0.19)pg/mg) were significantly lower than those in the surgery group((145.10±6.46)pg/mg, (5.67±0.43)pg/mg, (27.88±3.43)pg/mg, (4.74±0.32)pg/mg, all P<0.01). Conclusion:Nobiletin can obviously alleviate POCD symptoms caused by sevoflurane inhalation anesthesia.

Abstract On April 25, 2021, a case with hookworm infections was identified during the surveillance of soil-borne nematodiasis by Tiantai Center for Disease Control and Prevention, Taizhou City, Zhejiang Province. The patients was admitted to a county people's hospital due to dizziness and limb weakness on July 24, 2020. Laboratory tests showed 2.5×1012/L red blood cell counts, 45 g/L hemoglobin, 3.4% eosinophil percentage, 4.7 μmol/L serum iron and <1 μg/L ferritin, and severe iron-deficiency anemia was initially diagnosed. Following treatment with blood transfusion and ion supplement, subsequent three routine blood tests indicated elevated eosinophil percentages. On April 25, 2021, hookworm eggs were detected in stool samples using Kate-Katz technique, and Necator americanus was identified with the test-tube filter-paper culture method. Severe iron-deficiency anemia caused by hookworm infections was diagnosed based on field epidemiological surveys and laboratory tests. The health education pertaining to parasitic disease control knowledge among residents and the diagnosis and treatment of parasitic diseases in medical institutions are recommended to be improved in rural areas to avoid misdiagnosis and missing diagnosis.

Objective:To observe the effects of continuous light exposure on skeletal muscle fiber type transformation and lipid metabolism, and to explore its internal relationship.Methods:Mice were randomly divided into normal light group and 24-hour continuous light group by random number table. The serum and skeletal muscle lipid content and urine 6-sulfatoxymelatonin(6-SML)level were detected by ELISA. The expression of circadian clock and lipid metabolism related genes mRNA were observed by realtime PCR. The muscle fiber type and lipid deposition were evaluated by tissue immunofluorescence as well as oil red O staining.Results:Compared with the normal light group, the level of 6-SML in urine at night decreased( P<0.05), and the expression level and rhythm of brain and muscle ARNT-like protein 1(Bmal1), circadian locomotor output cycles protein kaput(Clock), and period 2(Per2)mRNA in the skeletal muscle changed in continuous light group. In addition, the body weight, blood lipid, free fatty acid, and triglyceride contents of skeletal muscle in continuous light group increased significantly( P<0.05 or P<0.01), the expression of carnitine palmitoyltransferase 1b (Cpt1b)mRNA, the key enzyme of fatty acid oxidation, decreased significantly( P<0.05), while the expression of stearoyl-CoA desaturase(Scd1)mRNA, a lipid synthesis related gene, increased significantly( P<0.01). Further immunofluorescence analysis showed that the proportion of slow muscle fibers decreased and that of fast muscle fibers increased in continuous light group(both P<0.05). Conclusion:The process of ectopic deposition of lipid in skeletal muscle in mice induced by continuous light exposure may be related to the remodeling of skeletal muscle fibers.

OBJECTIVE：To reevaluate the guidelines/cons ensus，systematic review/Meta-analysis of proton pump inhibitors （PPIs）in the prevention of drug-induced gastrointestinal injury ，and to provide evidence-based reference for its clinical use. METHODS： The relevant guidelines/consensus and systematic review/Meta-analysis literatures at home and abroad were systematically reviewed ，and the re evaluation was carried out from the effectiveness ，safety and economy dimensions to analyze the current situation of clinical use of PPIs in the prevention of drug-induced gastrointestinal injury in adults and children. RESULTS ： A total of 14 clinical guidelines/consensus and 10 systematic review/Meta-analysis literatures of PPIs for the prevention of drug-related gastrointestinal injury at home and abroad were sorted out and included. In terms of effectiveness ，PPIs could prevent various drug-related gastric mucosal damage ，gastrointestinal bleeding and other damage to the digestive tract ，but PPIs had not yet obtained the indication for children in China ；PPIs were widely used in the treatment of children ’s digestive tract diseases ，which belonged to off-label medication. In terms of safety ，the common adverse reactions of PPIs included headache ，gastrointestinal symptoms，etc. There may be risks of kidney disease and fracture during long-term application. In terms of economy ，for some patients with digestive tract and cardiovascular disease risk ，the economic benefit of NSAIDs combined with PPIs were higher ； esomeprazole 20 mg and 40 mg daily were equally effective in preventing ulcer recurrence caused by NSAIDs ，but increasing the dose could not improve the preventive effect. CONCLUSIONS ：The preventive effect of PPIs on drug-induced gastrointestinal injury is supported by evidence-based evidence. It has good safety in adults and has certain economic benefits ；but it belongs to off-label drug use in children in China ，and the safety and economy still need to refer to the results of adult studies. In the future ，a number of multicenter prospective clinical studies based on Chinese pediatric population are still needed to provide more support for the prevention and treatment of drug-induced gastrointestinal injury by PPIs in children.

ObjectiveTo investigate the effect of Rehmanniae Radix Praeparata on neurological function injury in ischemic stroke rats and explore its mechanism. MethodMale SD rats were randomized into sham operation， model， low- and high -dose （3.5 g·kg^-1 and 7 g·kg^-1） Rehmannia Radix Praeparata， and nimodipine （0.01 g·kg^-1） groups. The rat model of middle cerebral artery occlusion （MCAO） was established with the modified suture occlusion method. Zea-Longa 5-point scoring was employed to evaluate the neurological function of rats. The cerebral infarction volume was detected by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Hematoxylin-eosin staining and Nissl staining were employed to observe the morphology and damage of the brain tissue. Meanwhile， the serum levels of lactate dehydrogenase （LDH）， oxidative stress-related indicators superoxide dismutase （SOD）， glutathione peroxidase 4 （GPX4）， and malondialdehyde （MDA）， and the iron （Fe） content in the brain tissue were determined. To explore the mechanism of Rehmanniae Radix Preparata in mitigating the neurological damage in ischemic stroke rats， Western blotting was employed to determine the expression levels of proteins in the ischemic brain tissue. The autophagy-associated proteins included autophagy effector （beclin-1）， microtubule-associated protein light chain 3 （LC3B）， and ubiquitin-binding protein p62 （p62）. The ferroptosis-associated proteins included transferrin （TF）， transferrin receptor 1 （TFR1）， ferritin heavy chain 1 （FTH1）， and ferropotin （FPN1）. The neurological function injury-associated proteins included brain-derived neurotrophic factor （BDNF） and tyrosine kinase receptor B （TrkB）. ResultCompared with the sham operation group， the model group showed increased neurological function score， cerebral infarction volume， and appearance of nuclear pyknosis and vacuole of cells in the cerebral cortex. In addition， the model group presented elevated levels of LDH， MDA， and Fe （P<0.01） and lowered levels of SOD and GPX4 （P<0.01）. Compared with the model group， Rehmanniae Radix Praeparata decreased the content of LDH， MDA， and Fe （P<0.05， P<0.01） and elevated the levels of SOD and GPX4 （P<0.05， P<0.01）. Compared with the sham operation group， the modeling promoted the expression of beclin-1，LC3B Ⅱ/Ⅰ， TF， and TFR1 and inhibited the expression of p62， FTH1， FPN1， BDNF， and TrkB （P<0.01）. The expression levels of these proteins were recovered after the treatment with Rehmanniae Radix Praeparata. ConclusionRehmanniae Radix Praeparata may inhibit ferroptosis and improve the neurological function in ischemic stroke rats by down-regulating the autophagy level in the brain tissue.