Starting from the intrinsic relationship between the glymphatic system and the core pathogenesis of vascular cognitive impairment （VCI）， including internal dampness， phlegm turbidity， and blood stasis， this paper explores clinical approaches to the diagnosis and treatment of VCI. Dysfunction of the kidney's role in governing water leads to the accumulation of dampness， phlegm turbidity， and blood stasis， which are key pathological mechanisms underlying the onset and progression of VCI. The glymphatic system participates in the circulation of cerebrospinal fluid within the central nervous system， and its impairment can result in reduced clearance of soluble metabolic waste products in the brain， a crucial factor contributing to VCI. It is proposed that the "kidney governing water" function is related to the glymphatic system， and that the cerebral collaterals correspond structurally to the glymphatic pathways. Clinically， therapies aimed at tonifying the kidney， resolving phlegm， activating blood circulation， and unblocking collaterals， such as modified Kaixin Powder （开心散）， which eliminates dampness and turbidity， transforms phlegm， restores consciousness， enhances cognition， and strengthens the brain， are commonly employed. These treatments may improve VCI prognosis by regulating glymphatic system function， providing a theoretical basis for the prevention and treatment of VCI with traditional Chinese medicine.

Objective To explore the effects of sodium oligomannate combined with high-frequency repetitive transcranial magnetic stimulation on the activity of daily living and intelligence level of patients with Alzheimer's disease.Methods A total of 100 patients with Alzheimer's disease admitted to Henan Provincial Staff Hospital from September 2021 to September 2023 were selected as the research subjects.These patients were divided into an observation group and a control group according to the random number table method,with 50 patients in each group.Patients in the control group were given high-frequency repetitive transcranial magnetic stimulation,and patients in the observation group were given sodium oligomannate combined with high-fre-quency repetitive transcranial magnetic stimulation.Enzyme-linked immunosorbent assay was used to detect the levels of amyloid β-protein(Aβ)142,tumor necrosis factor-a(TNF-a)and interleukin-6(IL-6)in patients of the two groups before and after treatment.Chemiluminescence was used to detect the levels of neurotransmitters in patients of the two groups before and after treatment.The mental symptoms of patients in the two groups before and after treatment were evaluated by the behavioral pathology in Alzheimer's disease rating scale,the intelligence level of patients in the two groups before and after treatment was evaluated by the mini-mental state examination(MMSE)scale and the Montreal cognitive assessment(MoCA)scale,the activity of daily living of patients in the two groups before and after treatment was evaluated by Alzheimer's disease cooperative study-activity of daily living(ADCS-ADL),and the quality of life of patients in the two groups before and after treatment was evaluated by the quality of life-Alzheimer's disease scale.Results Before treatment,the two groups showed no significant difference in the levels of Aβ1-42,TNF-α and IL-6(P＞0.05);after treatment,the levels of Aβ1-42,TNF-α and IL-6 in both groups were lower than those before treatment,and the levels of Aβ1-42,TNF-α and IL-6 in the observation group were lower than those in the control group(P＜0.05).Before treatment,there were no statistically significant differences in the levels of 5-hydroxytryptamine(5-HT),acetylcholine(ACh),γ-aminobutyric acid(GABA),and Alzheimer-associated neuronal thread protein(AD7c-NTP)between the two groups(P＞0.05);after treatment,the levels of 5-HT,ACh,and GABA in the two groups were higher than those before treatment,while the AD7c-NTP level was lower than that before treatment(P＜0.05);after treatment,the levels of 5-HT,ACh,and GABA in the observation group were higher than those in the control group,while the AD7c-NTP level was lower than that in the control group(P＜0.05).Before treatment,there were no significant differe-nces in the scores of paranoid and delusional ideas,hallucinations,behavioral disorders,aggressive behaviors,daily rhythm disorders,emotional disorders,anxiety and fear,and the total scores between the two groups(P＞0.05);after treatment,the scores of paranoid and delusional ideas,hallucinations,behavioral disorders,aggressive behaviors,daily rhythm disorders,emotional disorders,anxiety and fear,and the total scores of patients in the two groups were lower than those before treatment,and the scores of paranoid and delusional ideas,hallucinations,behavioral disorders,aggressive behaviors,daily rhythm disorders,emotional disorders,anxiety and fear,and the total scores of patients in the observation group were lower than those in the control group(P＜0.05).Before treatment,there were no significant differences in MMSE,MoCA and ADCS-ADL scores of patients between the two groups(P＞0.05);after treatment,the MMSE,MoCA and ADCS-ADL scores of patientsin the two groups were higher than those before treatment,and the MMSE,MoCA and ADCS-ADL scores of patientsin the observation group were higher than those in the control group(P＜0.05).Before treatment,there were no significant differences in the scores of physiological function,mental function,behavioral ability and interpersonal relationship,and the total scores of patients between the two groups(P＞0.05).After treatment,the scores of physiological function,mental function,behavioral ability and interpersonal relationship,and the total scores of patients in the two groups were higher than those before treatment,and the scores of physiological function,mental function,behavioral ability and interpersonal relationship,and the total scores of patients in the observation group were higher than those in the control group(P＜0.05).Conclusion Sodium oligomannate combined with high-frequency repetitive transcranial magnetic stimulation can improve the inflammatory state of patients with Alzheimer's disease,regulate neurotransmitter levels,alleviate psychiatric symptoms,enhance the intelligence level and the activity of daily living,and increase the quality of life.

Objective:To evaluate the effectiveness of oral-nasal oxygen supply mouth guard in painless gastroscopy for snoring patients.Methods:The snoring patients who underwent painless gastroscopy at two Endoscopy Centers of Shanghai East Hospital, Tongji University in July 2022 were randomly divided into the observation group (using oral-nasal oxygen supply mouth guard) and the control group (using ordinary nasal oxygen tube and mouth guard). Parameters such as the wearing time and the removal time of the mouth guard, lowest pulse oxygen saturation (SpO 2), incidence of hypoxemia, and the satisfaction of medical staff were compared between the two groups. Results:The wearing time of mouth guard was 11.63±0.84 seconds and the removal time was 5.33±0.76 seconds in the observation group ( n=40), which were lower than those in the control group ( n=47) (14.91±1.21 seconds, t=-14.463, P<0.001; 10.38±0.80 seconds, t=-30.095, P<0.001). The wearing satisfaction score was 9.80±0.61, the lowest SpO 2 was (96.70±3.42)%, the removal satisfaction score was 9.75±0.67, and the anesthesiologists' satisfaction score was 9.20±1.42 in the observation group, which were higher than those in the control group [7.70±0.93, t=12.209, P<0.001; (94.06±3.72)%, t=3.417, P=0.001; 7.96±0.98, t=9.803, P<0.001; 8.13±1.35, t=3.615, P=0.001] with significant difference. There was no significant difference in the incidence of hypoxemia [10.00% (4/40) VS 14.89% (7/47), χ2=0.130, P=0.718] and endoscopic physician satisfaction score (9.30±0.97 VS 9.02±1.31, t=1.112, P=0.269) between the two groups. Conclusion:The oral-nasal oxygen supply mouth guard is easy to wear and remove, effectively reducing SpO 2 fluctuations during painless gastroscopy for snoring patients. It can enhance medical staff satisfaction with high clinical value.

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.

Objective : The differences of cognitive impairment between children with attention deficit hyperactivity disorder (ADHD) and normal children were compared , the influencing factors of cognitive impairment of children with ADHD were analyzed . Methods : A total of 133 children with ADHD were selected as the ADHD group , and 117 normal children were recruited as the control group . The severity of the subjects ′ clinical symptoms was assessed using the Swanson , Nolan , & Pelham Rating Scale⁃Fourth Edition ( SNAP⁃IV) and the Weiss Functional Impairment Rating Scale . The degree of cognitive functional impairment of subjects was assessed using the MATRICS cognitive suite (MCBB) , and the executive function impairment of the subjects was assessed by the Behavior Rating Inventory of Executive Function ( BRIEF) . The differences in cognitive functional impairment of the two groups were compared . The children with ADHD were further divided into three groups according to their clinical phenotype and age , respectively , and the differences of cognitive impairment among the three groups were compared . The influencing factors of the degree of cognitive impairment in children with ADHD were analyzed by multiple linear regression . The improvement of methylphenidate sustained⁃release tablets on cognitive and executive functional impairment in children with ADHD was observed . Results : The scores of SNAP⁃IV , Weiss Functional Impairment Rating Scale , connection test and BRIEF of ADHD patients were significantly higher than those of normal controls (P < 0. 05) . The scores of symbol coding test and maze test of ADHD patients were significantly lower than those of normal controls (P < 0. 05) . The score of symbol encoding test in children with ADHD⁃HI was significantly higher than that in ADHD⁃I and ADHD⁃C groups (P < 0. 05) , and the total BRIEF score of ADHD⁃C was significantly higher than that in ADHD⁃I and ADHD⁃HI groups (P < 0. 05) . With the increase of age , the score of connection test of ADHD children gradually decreased , while the scores of symbol coding test and maze test gradually increased (P < 0. 05) . The results of multiple linear regression analysis showed that age was the influencing factor of ADHD children ′s score in the connection test , symbol coding test and maze test (P < 0. 05) ; the scores of SNAP⁃IV and Weiss Functional Impairment Rating Scale were the influencing factors of BRIEF score of ADHD children (P < 0. 05) . After methylphenidate treatment , the scores of connection testand BRIEF significantly decreased (P < 0. 001) , while the scores of symbol coding test and maze test significantly increased (P < 0. 001) . Conclusion The younger the age and the more serious the clinical symptoms related to ADHD suggest that the cognitive impairment of children with ADHD is more serious . After methylphenidate treatment , the degree of cognitive and executive impairment in children with ADHD are improved .

ObjectiveTo explore the mechanism of Qigesan （QGS） in intervening in the migration and invasion of esophageal carcinoma TE-1 cells. MethodMicroarray technology was used to screen differentially expressed genes （DEGs） in the normal group and the QGS group， and the ontological functions and signaling pathways of DEGs were analyzed. The thiazolyl tetrazolium （MTT） assay was used to detect the effect of QGS on the viability of TE-1 cells. In the subsequent experiments for verification， a blank group， a transforming growth factor-β₁ （TGF-β₁） group， a TGF-β₁ + QGS group， and a TGF-β₁ + SB431542 group were set up. The cell morphology in each experimental group was observed by microscopy. The migration and invasion abilities of cells were detected by wound healing assay， and the mRNA expression levels of E-Cadherin， vimentin， Smad2， and Smad7 were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of E-Cadherin， vimentin， p-Smad2/3， Smad2/3， and Smad7 was detected by Western blot. ResultThere were 1 487 DEGs between the QGS group and the blank group， including 1 080 down-regulated ones （accounting for 72.63%） and 407 up-regulated ones. The down-regulated genes were mainly involved in biological processes such as cytoskeletal protein binding， ATP binding， adenylate nucleotide binding， and adenylate ribonucleotide binding， and the involved Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways included TGF-β signaling pathway， cell cycle， extracellular matrix-receptor interaction protein， tumor pathways， and oocyte meiosis. The up-regulated genes were mainly involved in RNA binding， DNA binding， transcriptional regulator activity， transcriptional activator activity， and nucleotide binding， and the KEGG pathways involved mainly included mitogen-activated protein kinase （MAPK） signaling pathway， bladder cancer， renal cell carcinoma， cancer pathways， and p53 signaling pathway. Compared with the blank group， the inhibition rate of cell viability of TE-1 cells increased after QGS （20， 30， 40， 60， 80 mg·L^-1） intervention for 12， 24， 36， 48， 60 h （P<0.05）， and the inhibition rate was time- and dose-dependent. Compared with the blank group， the TGF-β₁ group showed lengthened cells with fibroblast phenotype. Compared with the TGF-β₁ group， the TGF-β₁ + QGS group showed shortened cells with normal morphology and epithelial phenotype. The cell morphology in the TGF-β₁ + SB431542 group was similar to that of the TGF-β₁ + QGS group. Compared with the blank group， the TGF-β₁ group showed potentiated ability of cell migration and invasion （P<0.05）. Compared with the TGF-β₁ group， the TGF-β₁ + QGS group and the TGF-β₁ + SB431542 group showed inhibited and weakened migration and invasion abilities of cells （P<0.05）. However， there was no significant difference in migration and invasion abilities between the TGF-β₁ + QGS group and the TGF-β₁ + SB431542 group. The mRNA expression levels of vimentin and Smad2 in the TGF-β₁ group were higher （P<0.05）， and the mRNA expression levels of E-Cadherin and Smad7 were lower （P<0.05） than those in the blank group. Compared with the TGF-β₁ group， the TGF-β₁ + QGS group and the TGF-β₁+ SB431542 group exhibited decreased expression levels of vimentin and Smad2 mRNA （P<0.05）， and elevated expression levels of E-Cadherin and Smad7 mRNA （P<0.05）. Compared with the blank group， the TGF-β₁ group showed up-regulated protein expression levels of vimentin， p-Smad2/3， and Smad2/3 （P<0.05）， and reduced protein expression levels of E-Cadherin and Smad7 （P<0.05）. Compared with the TGF-β₁ group， the TGF-β₁ + QGS group and the TGF-β₁ + SB431542 group displayed decreased protein expression levels of vimentin， p-Smad2/3， and Smad2/3 （P<0.05）， and increased protein expression levels of E-Cadherin and Smad7 （P<0.05）. ConclusionThe ethyl acetate extract of QGS inhibits the epithelial-mesenchymal transition （EMT） of TE-1 cells through the TGF-β₁ pathway to reduce the migration and invasion of TE-1 cells.

Objective To explore the antitussive action site and potential mechanism of Shegan Zhike Capsule.Methods The mouse cough model induced by concentrated ammonia was used to observe the dose effect relationship of the antitussive effect of Shegan Zhike capsule.The central antitussive effect of Shegan Zhike capsule was observed by using the cough model induced by electrical stimulation of superior laryngeal nerve in guinea pigs.The peripheral antitussive effect of Shegan Zhike capsule was observed by using the cough model of capsaicin desensitized guinea pigs induced by mechanical stimulation.The model of chronic bronchitis in guinea pigs was established by smoking,and the effects of Shegan Zhike Capsule on vasoactive amines histamine(HA)and 5-hydroxytryptamine(5-HT)were observed.Results Shegan Zhike capsule could significantly reduce the number of coughs in mice at the doses of 43.00,86.00 and 172.00 mg extract·kg-1(P<0.05 or P<0.01).The low-dose group,the middle-dose group,and the high-dose group of Shegan Zhike Capsule did not significantly inhibit the cough inducing effect of electrical stimulation of guinea pig superior laryngeal nerve at 30 min and 60 min after administration.Shegan Zhike capsule could significantly inhibit the cough of capsaicin desensitized guinea pigs caused by mechanical stimulation in the low dose group at 60 min,the medium dose group at 30 min and the high dose group at 30 min and 60 min(P<0.05).Compared with the model control group,the content of HA in serum of guinea pigs in low,medium and high dose groups of Shegan Zhike capsule decreased significantly(P<0.05 or P<0.01).The content of serum 5-HT in the high dose group decreased significantly(P<0.05).Conclusion The antitussive effect of Shegan Zhike Capsule was not in the center,and its peripheral antitussive effect was related to the inhibition of RARs receptors,and vasoactive amines such as HA and 5-HT were also involved.

O'Sullivan-Mcleod syndrome is a very rare variant of MND with a good prognosis. Its clinical feature is distal lower motor neuron syndrome of both upper limbs, and there is no effective treatment at present. We reported a case of O'Sullivan-Mcleod syndrome in this paper.The patient exhibited with middle-aged progressive distal muscle weakness and atrophy of both upper limbs, without sensory, cognitive or behavioral impairment and without pyramidal tract sign. Laboratory examination, imaging and genetic tests showed no obvious abnormalities. EMG revealed neurogenic damage to the small muscles of both hands. Now we retrospectively analyzed the clinical features of a patient with O'Sullivan-McLeod syndrome, and data from 18 cases for comparative analysis, in order to improve its understanding by clinicians.