Lipid rafts are microdomains in the cell membrane that are involved in cell signal transduction,metabolism,and intercellu-lar interactions.In recent years,studies have shown that lipid rafts play an important role in the pathogenesis of diabetes.Cholesterol and sphingolipids are the main lipid components in lipid rafts,and the protein components in lipid rafts include caveolin,flotillin,pal-mitoylated proteins,and glycosylphosphatidylinositol-anchored proteins.Changes in these components affect the structure and function of lipid rafts,which in turn may affect insulin signal transduction,leading to the occurrence of diabetes-related diseases.Lipid rafts are closely related to the occurrence and development of diabetes in different tissues.Pancreatic lipid rafts are closely related to insulin se-cretion,and their structural changes affect insulin synthesis and release.Changes in lipid rafts in adipose tissue are related to insulin resistance and disorders of glycolipid metabolism.Changes in lipid rafts in the liver can affect gluconeogenesis and glycogen synthesis.Lipid rafts in the kidney play a regulatory role in the progression of diabetic nephropathy.This article aims to provide a comprehensive overview of the role of lipid rafts in the pathogenesis of diabetes,offering insights into the identification of new targets for the prevention and treatment of diabetes in the future,as well as presenting a new perspective for the development of therapeutic agents for diabetes.

Objective To explore the clinical efficacy of laser-assisted sclerectomy and cataract extraction combined with angle separation in the treatment of angle-closure glaucoma.Methods A total of 162 patients with angle closure glaucoma were selected as the research subjects.Eighty-one patients in the experimental group under-went laser-assisted sclerectomy and cataract extraction combined with angle separation,and another 81 patients in the control group underwent cataract extraction combined with angle separation.The therapeutic effects of two groups of patients were observed.Results The postoperative visual acuity,BCVA,angle width,and corneal endothelial cell count of the experimental group were higher than those of the control group,but the intraocular pressure,central anterior chamber depth,and corneal thickness were all lower than those in the control group.The incidence of adverse reactions in the experimental group(6.2% )was lower than that in the control group(13.6% ).During postop-erative follow-up,there was no further increase in intraocular pressure in the two groups,while the height of filtering blebs in the control group decreased significantly when compared with that in the experimental group.One month after surgery,the BCVA and corneal endothelial cell count in the experimental group were higher than those in the control group(P<0.05),and the corneal thickness was lower than that in the control group(P<0.05),but no statistical significance was found at 3 and 6 months after surgery.The astigmatism in the experimental group was better than that in the control group 3 months after surgery,but there was no statistically significant difference at 1 month and 6 months after surgery.Conclusion Laser-assisted sclerectomy and cataract extraction combined with angle separa-tion are effective and safe in the treatment of angle closure glaucoma.

Objective To investigate the correlation between lung Point-of-Care ultrasound score and clinical indicators by analyzing the features of Point-of-Care ultrasound in acute COVID-19.Methods 30 COVID-19 patients admitted to the Affili-ated Hospital of North Sichuan Medical College were selected,lung Point-of-Care ultrasound sequential scan was conducted in pa-tients with the BLUE-PLUS regimen and the lung Point-of-Care ultrasound semi-quantitative scoring was performed.The clinical indicators of partial pressure of carbon dioxide,anion gap,PH value,standard bicarbonate,oxygen partial pressure,oxygen satu-ration,the lymphocyte percentage(LYM% ),the lymphocytic absolute value(LYM#),the clinical typing,hospital stay,etc were collected.The lung Point-of-Care ultrasound score of acute COVID-19 patients in different clinical typing was compared and the features of Point-of-Care ultrasound in acute COVID-19 were analyzed.The ROC curve was constructed to analyze the effec-tiveness of lung Point-of-Care ultrasound score for the typing of normal type and(critical)severe type.Results In 30 cases of COVID-19 patients during the acute period,there were 29 patients with at least one lung point involvement on both sides(96.7% ),1 case with at least one lung point involvement on one side(3.3% )and 15 cases showed Lung consolidation＞1cm at least one lung point.Comparison of the same lung point between the left and right lung was performed and there was statistical-ly significant difference in the total scores between the left and right lung(P＜0.05).Comparison of total scores of different lung points in patients with different clinical types showed there was statistically significant difference in the total scores of left lung,the total scores of right lung,the total scores of whole lung between normal type and critical type(P＜0.05).The area under the curve(AUC)for the diagnosis of normal and(critical)severe types based on the total lung scores is 0.870.The total scores of the left lung,right lung,and whole lung were not correlated with LYM% ,LYM#,and anion gap(P＞0.05)were positively cor-related with clinical typing and hospital stay,and negatively correlated with standard bicarbonate(P＜0.05).The total scores of the left lung and whole lung were negatively correlated with PH value,oxygen partial pressure,and oxygen saturation,but posi-tively correlated with partial pressure of carbon dioxide(P＜0.05).The total scores of the right lung was not correlated with PH value,partial pressure of carbon dioxide,oxygen partial pressure,and oxygen saturation(P＞0.05).Conclusion There were differences in Point-of-Care ultrasound features among patients with different clinical types of acute COVID-19,Lung Point-of-Care ultrasound semi-quantitative scoring is correlated with pH value,partial pressure of carbon dioxide,standard bicarbonate,ox-ygen partial pressure,oxygen saturation,clinical typing and hospital stay.The patients of critical type have higher scores,lung Point-of-Care ultrasound is expected to be used for clinical typing and condition evaluation of acute COVID-19 patients.

Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6～8 weeks old and weighing from 180～220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.

Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activ-ity while high concentration of IC50 at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.

Objective To study the distribution and drug resistance characteristics of pathogenic bacteria in the elderly population of China by collecting and analyzing the standardized case data on the pathogens of infections in elderly patients,and to facilitate the establishment of a standardized layered surveillance system for pathogenic bacteria in China.Methods We collected the case data of elderly patients(≥65 years old)from 62 sentinel hospitals across the country in 2021.Then,we statistically analyzed the data by patient age,their geographical region,the distribution of pathogenic bacteria,and the drug resistance characteristics of main pathogens.Results A total of 3468 cases from across the country were included in the study.The top three sources of patients were the intensive care unit(13.2%),the department of respiratory medicine(11.2%),and the department of general surgery(8.4%).The top three types of specimens were urine(25.5%),sputum(20.6%),and blood(18.7%).A total of 3468 strains of pathogens were isolated,among which,78.9%were gram-negative bacteria and 21.1%were gram-positive bacteria.The top five types of bacteria were Escherichia coli(20.9%),Klebsiella pneumoniae(18.3%),Pseudomonas aeruginosa(11.2%),Staphylococcus aureus(9.0%),and Acinetobacter baumannii(7.0%).The isolation rates of common important drug-resistant bacteria were 38.0%for methicillin-resistant Staphylococcus aureus(MRSA),68.7%for carbapenem-resistant Acinetobacter baumannii(CRAB),and 38.2%for carbapenem-resistant Pseudomonas aeruginosa(CRPA),20.1%for carbapenem-resistant Klebsiella pneumoniae(CRKP),5.2%for carbapenem-resistant Escherichia coli(CRECO),and 2.1%for vancomycin-resistant Enterococcus(VRE).There were differences in the isolation rates of CRAB and CRKP in clinical care in the elderly population in seven geographical regions of China(P＜0.05).Klebsiella pneumoniae is the most important pathogen in the elderly population≥85 years old,and the isolation rates of CRKP showed significant differences in different age groups(P＜0.05).Conclusion There are significant differences in the drug resistance of pathogenic bacteria in the elderly populations of different regions and age groups in China.Therefore,monitoring the distribution and drug resistance of pathogenic bacteria in the elderly population and formulating targeted treatment plans according to the characteristics of the specific regions and age groups are of great significance to the improvement in the treatment outcomes and prognosis of the elderly population.

Amyloid-related imaging abnormalities(ARIA),intracranial signal abnormalities observed in magnetic resonance imaging(MRI),represent one of the main adverse events associated with treating Alzheimer's disease(AD)with anti-amyloid-β(anti-Aβ)monoclonal antibodies.In severe cases,patients'lives may be threatened.As the first anti-Aβ antibody was approved for use in China,clinical departments are now confronted with an increased likelihood of encountering ARIA in real-world scenarios.Accurate pre-treatment risk assessment,timely identification during medication,and severity evaluation of ARIA are of great significance in guiding clinical decisions.The identification and assessment of ARIA can be conducted from two perspectives—imaging and clinical symptoms.This article focuses on imaging.We reviewed the pathophysiological mechanisms,epidemiological and clinical characteristics,and imaging protocols and assessment of ARIA.We also stated at the end of the review that most current research data on ARIA came from clinical drug trials involving Caucasian populations,and that there was a lack of treatment experience in the real-world application of anti-Aβ monoclonal antibodies in Chinese populations.Many issues concerning pre-treatment risk assessment still need to be explored.Additionally,whether there are other clinical factors and imaging indicators that can help predict drug risks,and whether using different imaging protocols can help make a difference in patient management in the real world all require further investigation.

Objective:To compare the differences of brain activation in patients with neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) under contact heat stimulation (CHS), and to explore the characteristics of pain-related brain networks in NMOSD and MS patients.Methods:Fourteen NMOSD patients (NMOSD group) and 12 MS patients (MS group) admitted to Affiliated Hospital of North Sichuan Medical College from September 2022 to December 2022 who met the diagnostic criteria were collected. Twelve healthy individuals (HC group) matched with gender and age were recruited during the same period. Visual Analogue Scale (VAS) score was used to evaluate the pain of the subjects, CHS painful stimuli were given, and task-state functional magnetic resonance imaging (fMRI) scans were performed at the same time, and the differences in brain activation among the 3 groups were analyzed and compared.Results:(1) Compared with the HC group, the NMOSD group had a stronger activation degree than the HC group in the brain regions including the cortex around the left distance fissure, bilateral medial superior frontal gyrus; the activation degree of the NMOSD group was weaker than that of the HC group in the brain areas including the left medial and paracingulate gyrus, right superior parietal gyrus, left postcentral gyrus, and right supplementary motor area (all P<0.05). (2) Compared with the HC group, the brain regions whose activation degree was weaker in the MS group included the left caudate nucleus, left medial and paracingulate gyrus, left paracentral lobule, right superior parietal gyrus, left postcentral gyrus, left precuneus, right supplementary motor area, right superior temporal gyrus and right thalamus, and there was no brain area in the MS group whose activation degree was stronger than that of the HC group (all P<0.05). (3) Compared with the MS group, the brain regions with stronger activation degree in the NMOSD group included the left perifissure cortex and right thalamus, but no brain regions with weaker activation degree were found in the NMOSD group (all P<0.05). (4) There was a correlation between somatic pain VAS scores and activation of the medial superior frontal gyrus in the NMOSD group ( r=0.66, P<0.05). Conclusions:The results of CHS-fMRI in the NMOSD group, MS group and HC group showed that multiple brain regions were activated, indicating that multiple brain regions were involved in the generation and processing of pain, and there was a pain-related brain network. Pain-related brain networks were altered in NMOSD patients and MS patients, and there were differences in pain-related brain networks between the two diseases.

Objective:To observe the changes in brain functional magnetic resonance imaging (fMRI) in migraine patients under olfactory stimuli and analyze the characteristics of olfactory-related brain networks.Methods:Twenty-seven migraine patients (migraine group) enrolled in the Department of Neurology, Affiliated Hospital of North Sichuan Medical College from January 2021 to January 2022 were included, and 20 healthy adults were recruited as control group during the same period. All subjects underwent synchronous fMRI scanning under olfactory task stimulation, and magnetic resonance imaging data processing was performed using SPM12 and Matlab2019b softwares, and statistical analysis was performed with SPSS 23.0 software.Results:The activated brain regions in the control group included the left cerebellum, left inferior temporal gyrus, left fusiform gyrus, right middle frontal gyrus, right anterior central gyrus, insula, right central sulcus, superior marginal gyrus, right lenticular putamen, middle cingulate gyrus, paracentral lobule, and superior parietal gyrus ( P<0.05). The activated brain regions in the migraine group included the left cerebellum, right fusiform gyrus, right inferior temporal gyrus, right anterior central gyrus, and right posterior central gyrus ( P<0.05). Compared with the control group, the activation intensity of the migraine group was weaker in the right insula, right middle frontal gyrus orbit, left inferior frontal gyrus orbit, right dorsolateral superior frontal gyrus, right superior temporal gyrus, right superior occipital gyrus, medial and paracingulate gyrus, and right superior parietal gyrus ( P<0.05). Conclusion:Migraine patients have multiple brain regions involved in olfactory processing and have specific olfactory-related brain networks.

The high-content image-based assay is commonly leveraged for identifying the pheno-typic impact of genetic perturbations in biology field.However,a persistent issue remains unsolved during experiments:the interferential technical noises caused by systematic errors(e.g.,tempera-ture,reagent concentration,and well location)are always mixed up with the real biological signals,leading to misinterpretation of any conclusion drawn.Here,we reported a mean teacher-based deep learning model(DeepNoise)that can disentangle biological signals from the experimental noises.Specifically,we aimed to classify the phenotypic impact of 1108 different genetic perturbations screened from 125,510 fluorescent microscopy images,which were totally unrecognizable by the human eye.We validated our model by participating in the Recursion Cellular Image Classification Challenge,and DeepNoise achieved an extremely high classification score(accuracy:99.596％),ranking the 2nd place among 866 participating groups.This promising result indicates the success-ful separation of biological and technical factors,which might help decrease the cost of treatment development and expedite the drug discovery process.The source code of DeepNoise is available at https://github.com/Scu-sen/Recursion-Cellular-Image-Classification-Challenge.