AIM: To study the perception of first-order grating acuity and second-order spatial contrast sensitivity in patients with monocular anisometropia amblyopia.METHODS:A total of 715 children(715 eyes)diagnosed as monocular anisometropia amblyopia in our hospital from January 2018 to December 2022 were collected as amblyopia group, and 745 children(745 eyes)with normal corrected visual acuity were collected. The best corrected visual acuity(BCVA), first-order grating acuity and/or second-order spatial contrast sensitivity were measured, repectively. The perception ability of amblyopia patients to first-order grating acuity and second-order spatial contrast sensitivity were analyzed.RESULTS:There were significant differences between amblyopia group and normal control group in the perception of first-order grating acuity(11.58±6.10 vs. 20.27±3.47, P<0.001)and second-order spatial contrast sensitivity(0.33±0.16 vs 0.12±0.04, P<0.001). And there were significant differences between mild-to-moderate amblyopia and severe amblyopia patients in first-order grating acuity(12.10±6.23 vs. 8.13±3.70, P<0.001)and second-order spatial contrast sensitivity(0.32±0.16 vs. 0.37±0.17, P<0.05).CONCLUSION: The first-order and second-order visual pathway of the cerebral cortex in children with monocular anisometropia amblyopia have different degrees of damage. The injury of severe amblyopia is more serious than that of mild-to-moderate amblyopia.

OBJECTIVE To evaluate the efficacy and safety of programmed death-1/programmed death-ligand 1 （PD-1/PD-L1） inhibitors combined with bevacizumab in the treatment of advanced non-small cell lung cancer （NSCLC） based on platinum- containing dual therapy. METHODS Retrieved from CNKI， Wanfang， VIP， Web of Science， PubMed and other Chinese and English databases， cohort studies or randomized controlled trial studies on the treatment of advanced NSCLC with platinum- containing double agents in combination with PD-1/PD-L1 inhibitors and bevacizumab （trial group） versus platinum-containing double agents with or without PD-1/PD-L1 inhibitor or bevacizumab （control group） were collected from the inception to April 25， 2024. After screening literature， extracting data and evaluating quality， meta-analysis and sensitivity analysis were performed by using RevMan 5.4.1 software. RESULTS A total of 15 pieces of literature were included， involving 13 clinical studies with a total of 3 282 patients. Compared with the control group， partial response rate [RR＝0.75，95%CI（0.68，0.82），P＜0.000 01]， complete response rate [RR＝0.47，95%CI（0.29，0.76），P＝0.002]， progressive disease rate [RR＝1.23，95%CI（1.11，1.37），P＜0.000 1]， objective response rate （ORR） [RR＝0.72，95%CI（0.67，0.79），P＜0.000 01] and disease control rate （DCR） [RR＝0.85， 95%CI （0.77，0.95），P＝0.003] were higher in the trial group. There was no statistically significant difference in the stable disease rate [RR＝1.25， 95%CI （0.86， 1.83）， P＝0.25] or overall adverse drug reaction incidence rate [RR＝0.95， 95%CI （0.90， 1.00）， P＝ 0.07] between the two groups of patients. Sensitivity analyses showed robust and reliable results for all outcome indicators. CONCLUSIONS PD-1/PD-L1 inhibitors combined with bevacizumab based on platinum-containing dual therapy in the treatment of advanced NSCLC can improve patients’ clinical benefits， such as ORR and DCR， without increasing the risk of adverse drug reaction.

Objective To observe the pathological changes of cerebellar injury in rats with alcoholism.Methods An animal model of chronic alcoholism was established in Wistar male rats by gavage of 50%edible alcohol at increasing doses for 4 weeks.The pathological changes of cerebellar injury in rats after alcoholism were observed using an optical mi-croscope and a transmission electron microscope.Results Optical microscopy in rats with alcoholism showed signifi-cantly reduced number of granule cells and Purkinje cells in the cerebellum,and significant cell degeneration,especially in Purkinje cells.Electron microscopy showed significantly reduced organelles,irregularly shaped nucleus,and unobvi-ous and irregularly shaped nucleolus in cerebellar capillary endothelial cells.Conclusion Alcoholism induces damages to the cerebellar cells and their ultrastructure,providing a basic theoretical basis for the resulting motor and cognitive dys-function.

Objective:To investigate the safety and efficacy of laparoscopic simultaneous bilateral adrenalectomy in treating ectopic ACTH syndrome (ACTH)caused by medullary thyroid carcinoma(MTC).Methods:A 56-year-old male patient was admitted after MTC surgery and 7 months of general fatigue. The patient had a history of two open thyroid surgeries for medullary thyroid carcinoma, with previous pathological reports indicating lymph node metastasis in the upper mediastinum and mediastinum, accompanied by weak cytoplasmic expression of ACTH and negative CRH staining. After the operation, the patient developed diabetes, hypertension, and hypokalemia. Upon admission, the patient presented with a blood pressure reading of 200/95 mmHg (1 mmHg = 0.133 kPa), a weight of 61.5 kg, a height of 160 cm, a body mass index (BMI)of 24.02 kg/cm 2, and a waist circumference of 83 cm. Laboratory tests revealed the following: blood potassium level of 2.71 mmol/L, blood calcium level of 1.47 mmol/L, parathyroid hormone level of 6.0 pg/ml, fasting blood glucose level of 10.51 mmol/L, glycated hemoglobin level of 8.2%, blood calcitonin level exceeding 2 000 pg/ml, and blood CEA level of 70.8 μg/L. The plasma ACTH levels at 8∶00, 16∶00, and 24∶00 were 189.0, 125.0, and 65.0 pg/ml, respectively. Serum cortisol levels at 08∶00, 16∶00, and 24∶00 were 429.30, 408.14, and 446.61 μg/L, respectively. The 24-hour urine free cortisol measurement was 1 200 μg, and after the midnight 1mg dexamethasone suppression test at 8∶00, the plasma ACTH level was 183.0 pg/ml, and the serum cortisol level was 538.27 μg/L. The aldosterone level in standing position after 2 hours was 8.2 pg/ml. There were no significant abnormality in catecholamine hormone detection or thyroid function in blood and urine samples. An 18F-FDG-PET/CT examination showed multiple lymph node metastases in the neck, while an abdominal CT scan revealed bilateral adrenal hyperplasia. Enhanced MRI revealed pituitary gland thinning, and lung CT and sputum culture examinations showed scattered multiple lung infections. After a multidisciplinary discussion, the patient was diagnosed with EAS, postoperative MTC metastasis, diabetes, hypertension, hypokalemia, pulmonary infection, mild anemia, liver dysfunction, hypoparathyroidism, and hypocalcemia. The patient were accepted laparoscopic bilateral adrenalectomy via an abdominal approach under general anesthesia. The left adrenal gland was removed first, followed by the right adrenal gland after repositioning. Results:The surgery was successful with a surgical duration of approximately 60 minutes and an intraoperative bleeding volume of about 20 ml. No surgical complications occurred during the perioperative period. Pathological examination confirmed nodular hyperplasia of the adrenal cortex and bilateral adrenal medullary hyperplasia with negative ACTH staining. After a 3-month postoperative follow-up, blood calcitonin levels remained above 2000 pg/ml. The blood ACTH levels at 1 week, 1 month, and 3 months after surgery were 183.0, 220.0, and 731.0 pg/ml, respectively. However, hypertension, diabetes, and hypokalemia rapidly improved. One month after surgery, blood pressure was 100/80 mmHg, fasting blood glucose was 4.4 mmol/L, and blood potassium was 3.87 mmol/L. Pulmonary infection showed improvement, and no adrenal crisis occurred. Glucocorticoid replacement therapy consisted of 20 mg of hydrocortisone tablets in the morning and 10 mg in the afternoon, and thyroid hormone replacement therapy involved daily administration of 100 μg of levothyroxine. Genetic testing revealed heterozygous mutations in the Ret gene. The patient is currently undergoing clinical trial treatment with Ret inhibitors.Conclusions:Based on the data from this case and existing literature reports, laparoscopic simultaneous bilateral adrenalectomy might be safe and effective treatment option for EAS caused by unresectable MTC metastasis. It can correct hypertension, diabetes, and hypokalemia and increase the opportunity for MTC treatment.

Objective:To evaluate the effect of sleep fragmentation on postoperative cognitive dysfunction (POCD) and hippocampal glutaminergic metabolism in aged mice anesthetized with isoflurane.Methods:Forty healthy SPF-grade male C57BL/6J mice, aged 18 months, weighing 20-30 g, were divided into 4 groups ( n= 10 each) by the random number table method: normal control group (group C), sleep fragmentation group (group SF), isoflurane anesthesia/surgery group (group I/S), and sleep fragmentation plus isoflurane anesthesia/surgery group (group SF+ I/S). Group C did not received any treatment. Group SF received sleep fragmentation for 24 h. The right carotid artery exposure was performed under isoflurane anesthesia in group I/S. Group SF+ I/S received isoflurane anesthesia/right carotid artery exposure at 24 h after sleep fragmentation. The metabolic levels of glutamate (Glu), glutamine (Gln), Glu/Gln complex (Glx), and N-acetylaspartate (NAA) and their ratio to creatine (Cr) were measured by in vivo 9.4T hydrogen proton magnetic resonance spectroscopy at 2 h after anaesthesia. Y maze and Morris water maze tests were used to evaluate the cognitive function at 1-7 days after surgery. The mice were sacrificed after the behavioral testing, brain tissues were immediately obtained, and the number of Nissl bodies and density of dendritic spines in the hippocampal CA1 region were measured by Nissl staining and Golgi staining, respectively. Results:Compared with group C, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr, Gln/Cr and Glx/Cr in the hippocampal CA1 region were increased, and the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in SF, I/S and SF+ I/S groups ( P<0.05). Compared with group SF and group I/S, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr and Glx/Cr in hippocampal CA1 region was increased, the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in group SF+ I/S ( P<0.05). Conclusions:Sleep fragmentation exacerbates POCD in aged mice anesthetized with isoflurane, and the mechanism is related to nerve injury induced by abnormality in hippocampal glutaminergic metabolism excitability.

L-glutamic acid is the world's largest bulk amino acid product that is widely used in the food, pharmaceutical and chemical industries. Using Corynebacterium glutamicum G01 as the starting strain, the fermentation by-product alanine content was firstly reduced by knocking out the gene encoding alanine aminotransferase (alaT), a major by-product related to alanine synthesis. Secondly, since the α-ketoglutarate node carbon flow plays an important role in glutamate synthesis, the ribosome-binding site (RBS) sequence optimization was used to reduce the activity of α-ketoglutarate dehydrogenase and enhance the glutamate anabolic flow. The endogenous conversion of α-ketoglutarate to glutamate was also enhanced by screening different glutamate dehydrogenase. Subsequently, the glutamate transporter was rationally desgined to improve the glutamate efflux capacity. Finally, the fermentation conditions of the strain constructed using the above strategy were optimized in 5 L fermenters by a gradient temperature increase combined with a batch replenishment strategy. The glutamic acid production reached (135.33±4.68) g/L, which was 41.2% higher than that of the original strain (96.53±2.32) g/L. The yield was 55.8%, which was 11.6% higher than that of the original strain (44.2%). The combined strategy improved the titer and the yield of glutamic acid, which provides a reference for the metabolic modification of glutamic acid producing strains.
Glutamic Acid ; Corynebacterium glutamicum/genetics* ; Ketoglutaric Acids ; Metabolic Engineering ; Alanine

Objective:To screen host cell proteins interacting with rotavirus nonstructural protein 2(NSP2) and provide a theoretical basis for the discovery of antiviral targets.Methods:E. coli BL21(DE3) was transformed with a recombinant plasmid NSP2-pGEX-6P-1 and induced by IPTG to express NSP2-GST. GST affinity chromatography was used to purify NSP2-GST and Western blot was performed for verification. NSP2-GST and GST proteins were used as targets to capture interacting proteins in MA104 cells via GST pull-down. After silver staining, differential proteins were screened by in-gel enzymatic hydrolysis and mass spectrometry. Protein pilot platform was used to filter peptides, and the names and the biological functions of the proteins were obtained by Paragon algorithm. The potential connection between the interacting proteins was demonstrated by protein interaction network diagrams and GO functional annotation analysis. Moreover, the molecular docking of the top three proteins with NPS2 was predicted using HDOCK server and verified by docking and confidence scores, so as to investigate the visual docking model between interacting proteins. Results:SDS-PAGE and Western blot showed the successful purification of the recombinant protein NSP2. Ten host proteins including PKM2, which might interact with NSP2, were identified by GST pull-down and protein profiling. GO analysis and interaction diagrams revealed that RPS4X, EZR, SUPT16H and EIF2S3 mediated molecular expression; PKM2, LDHA and ATP5A1 participated in energy metabolism; HSP90, ACTB and ANXA2 were involved in biological movement. Besides, there were functional connections and interaction networks among them. Molecular docking further verified PKM2, HSP90 and RPS4X did interact with NSP2, and the interaction force were strong enough to form a stable structure.Conclusions:This study successfully discovered several host proteins including PKM2, HSP90 and RPS4X that could interact with NSP2, providing reference for investigating the process of rotavirus infection and making related prevention and control strategies.

Restless legs syndrome is a common motor-sensory disease of the nervous system. The main manifestations are an urge to move the legs, usually accompanied by or thought to be caused by uncomfortable and unpleasant sensations in the legs. These symptoms may begin or worsen during periods of rest or inactivity such as lying down or sitting and be partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues. This article will systematically review the pathogenesis, clinical manifestations, diagnostic criteria, differential diagnosis and treatment of restless legs syndrome.

Objective　To investigate the ultrastructural changes of brain vessels and cells after alcoholism in rats and the underlying mechanisms.Methods　Wistar male rats were given alcohol intragastrically for 4 weeks to induce chronic alcoholism model.To observe the ultrastructural changes related to brain vascular and cells damage after alcohol intoxication in rats by a transmission electron microscope.Results　The shape of cerebellar capillary endothelial cells was irregular in the alcohol intoxication group，there were fewer organelles in the cytoplasm.The nuclei are irregularly shaped,the nuclei are not obvious,irregular shape.The mitochondria in the frontal lobes are swollen,crest fracture,reduced number,the ribosomes attached to the crest fall off.The tubular rough endoplasmic reticulum is fractured,the interval between each other is widened,the quantity is reduced,the ribosomes attached to the outer surface of the tube membrane fall off.Mild demyelinating changes were observed in the hippocampus,and the lamellar myelin sheath composed of multiple plasma membranes was slightly detached and damaged.Conclusion　Alcoholism can cause the change and damage of the ultrastructure of cerebrovascular and related cells.To provide basic research theories and ideas for subsequent prevention and treatment.

Objective　To analyze the use of drugs andinfluencing factors of objective sleep disturbance among chronic insomnia patientsand to provide some normalization reference for clinical drug use. Methods　357 patients with definite chronic insomnia were selected. All patients were assessed with the Symptom Checklist （SCL-90），Hamilton Anxiety Scale （HAMA），Hamilton Depression Scale （HAMD），Pittsburgh sleep quality index （PSQI），Epworth sleepiness scale （ESS）. Polysomnography was used to evaluate objective sleep quality. Results　（1）The use of sedative and hypnotic drugs and other drugs that may affect sleep in the past 1 month before the first visit to the Sleep Center of our hospital was 53.50% for no drugs，46.5% for drugs and 18.21% for BzRAs among them. （2） The ESS scores of pharmacologic-therapy group was significantly lower than those in no-drugs group （Z=-2.463，P=0.014）. The total time sleep（Z=-3.521，P<0.001），Sleep efficiency（Z=-3.164，P=0.002），R%（Z=-3.044，P=0.003）were both significantly lower than those in no-drugs group. （3）The multivariate logistic regression results showed male （OR=1.938，95%CI 1.071～3.505，P=0.029），highly educated（OR=2.222，95%CI 1.196～4.130，P=0.012），anxiety state（OR=2.029，95%CI 1.018～4.043，P=0.044） and medication history（OR=1.974，95%CI 1.091～3.573，P=0.025） were the factors influencing SL>30 min. Age is the common factors for WASO>30 min（OR=1.052，95%CI 1.023～1.082，P<0.001），WASO>60 min（OR=1.068，95%CI 1.046～1.091，P<0.001） and SL>30 min and/or WASO>60 min （OR=1.068，95%CI 1.046～1.091，P<0.001）. Conclusion　Some patients have a high percentage of sleep-related medications before their first visit in our center，Most used was benzodiazepine receptor agonists. Gender，education，anxiety state and medication historywere the factors influencingsleep latency. Age is the common factors for difficulty maintaining sleep.