Alzheimer’s disease (AD) is one of the most common and severe dementias, severely affecting the physical and mental health and quality of life of patients and imposing a heavy burden on society. Recently, transcranial electrical stimulation (tES) has shown great potential for improving cognitive function in AD. Transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) are the two main forms of tES. The present review mainly summarizes the neuromolecular mechanisms of tDCS and tACS for the improvement of AD. Both techniques show similarities in exerting neuroprotective effects, improving cerebral blood flow to alleviate cerebrovascular dysfunction, affecting the state and function of astrocytes, affecting the levels of amyloid β‑protein (Aβ) and phosphorylated tau (p-tau) proteins, and affecting neuroplasticity. Specifically, tDCS improves neuronal status, inhibits neuronal apoptosis, improves cholinergic neurons and reduces oxidative stress, etc., and further exerts neuroprotective effects, but tACS mainly maintains the normal function of cholinergic neurons to exert the effects. For the alleviation of cerebrovascular dysfunction, tDCS has particular advantages in optimizing the neural vascular unit and improving the blood-brain barrier. For astrocytes, tDCS attenuates inflammatory responses by inhibiting their activation. In contrast, the effect of tACS on the activation state of microglial cells is still controversial for enhancement in AD mice and inhibition in patients. For Aβ levels, the effects of tDCS in AD patients are also inconclusive, but in AD rodents, tDCS may regulate molecular pathways related to Aβ production and degradation, thereby removing Aβ. In addition, tACS reduces p-tau levels in AD patients, but tDCS shows a trend toward reduction. In short, the effect of tES on Aβ and p-tau needs further investigation. Regarding neuroplasticity, tDCS improves cortical and synaptic plasticity, but tACS improves only synaptic plasticity. However, both techniques do not affect the molecular level associated with plasticity. On the other hand, this review has summarized some interesting findings of tES in non-AD rodents that may be relevant to the pathological mechanisms of AD. For neuroprotection, tDCS can promote neurogenesis, GABAergic and glutamatergic neurotransmission, modulate neuroprotection-related signaling pathways, reduce oxidative stress, and protect hippocampal neurons. In addition, tDCS inhibits conversion of microglia to the M1 phenotype and promotes conversion to the M2 phenotype, thereby reducing neuroinflammation. Importantly, tDCS induces changes in molecular indices associated with synaptic plasticity. These findings in non-AD rodents provide a reference for understanding the potential effect and possible mechanism of tES in AD and for exploring new approaches to treat other diseases with similar pathological features. In addition, tES has shown some effects in AD rodents, such as tACS improving plasticity, that have not been studied in non-AD rodents. These effects suggest the particular complexity of the pathological mechanisms of AD, which should be considered when applying the results of tES studies in non-AD rodents to AD rodents. In conclusion, this review provides a comprehensive overview of the neuromolecular mechanisms of tES in AD research and highlights its promise as a non-invasive brain stimulation technique in the treatment of AD. Furthermore, tES will play an indispensable role in the treatment of neuropsychiatric disorders and in the study of brain function.

ObjectiveTo observe the clinical efficacy of Gandou Fumu Granules （GDFMG） combined with sodium dimercaptosulphonate （DMPS） on liver fibrosis in Wilson disease （WD） patients with the syndrome of phlegm and blood stasis， evaluate its effect on cuproptosis-related indicators， and explore the possible mechanisms of cuproptosis in WD-related liver fibrosis. MethodsSixty WD patients diagnosed with the syndrome of phlegm and blood stasis between January 2023 and December 2023 were randomly divided into a control group and an observation group， with 30 patients in each group. The control group received the copper chelator DMPS for the first 6 days， followed by calcium gluconate injection for the next 2 days， completing an 8-day treatment cycle. The observation group received GDFMG in addition to the treatment regimen of the control group， with both groups treated for 21 cycles. A Beckman fully automated biochemical analyzer was used to detect levels of type Ⅳ collagen （CⅣ）， hyaluronic acid （HA）， laminin （LN）， N-terminal propeptide of type Ⅲ procollagen （PⅢ-NP）， and serum copper （SCu） before and after treatment in both groups. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of ferredoxin 1 （FDX1）， lipoic acid synthetase （LIAS）， and dihydrolipoamide S-acetyltransferase （DLAT）. Atomic absorption spectroscopy measured 24-hour urine copper levels before treatment and after the 7， 14， and 21 treatment cycles in both groups. An Fibro Touch （FT） non-invasive liver fibrosis diagnostic device was used to measure liver stiffness （LSM） in both groups before and after treatment. Traditional Chinese medicine syndrome score （TCMSS） was evaluated at the same intervals. Clinical efficacy， adverse events， and safety indicators were also compared. ResultsAfter treatment， levels of CⅣ， HA， LN， and PⅢNP significantly decreased in both groups compared to pre-treatment levels （P<0.01）. The observation group showed a more pronounced reduction compared to the control group （P<0.05）. There were no statistically significant differences in SCu levels in both groups before and after treatment. After treatment， levels of FDX1，LIAS and DLAT significantly increased in both groups（P<0.01）. The observation group showed more notable improvements in these indicators than the control group （P<0.05）. After the 7， 14， 21 treatment cycles， 24-hour urine copper levels significantly increased in both groups compared to pre-treatment levels （P<0.01）. The observation group had a greater increase in 24-hour urine copper levels than the control group after treatment （P<0.05，P<0.01）， and although 24-hour urine copper levels increased after 7 cycles， a gradual decline was observed in subsequent cycles. After treatment， LSM levels significantly decreased in both groups compared to pre-treatment levels （P<0.01）， with the observation group showing a greater reduction than the control group （P<0.05）. Clinical efficacy was significantly better in the observation group than the control group （P<0.05）. No significant differences in the incidence of adverse events or safety indicators were observed between the two groups after treatment. ConclusionGDFMG combined with DMPS can reduce LSM in WD patients with liver fibrosis and the syndrome of phlegm and blood stasis， inhibit cuproptosis， and improve clinical efficacy.

OBJECTIVE To explore comprehensive management and potential issues associated with long-term prescriptions medications of psychiatry， in order to provide a reference for the comprehensive management of long-term prescriptions of psychiatry in psychiatric hospitals and other medical institutions’ pharmacies. METHODS Starting from the applicable principles for long-term prescriptions of psychiatry， this study introduced the standardized assessment and precautions before issuing long-term prescriptions， the formulation and adjustment of the drug list， as well as the rational management of the long-term prescriptions. It also analyzed potential issues that may arise in the comprehensive management of long-term prescription medications and proposed corresponding countermeasures and suggestions. RESULTS & CONCLUSIONS Prior to initiating long-term prescriptions， a standardized assessment should be conducted on patients from the aspects of their psychiatric condition and long-term potential risk factors， pharmacological treatment plans and other non-pharmacological therapies， physical illnesses. Additionally， healthcare providers should fulfill their obligation to inform patients or their family members. The comprehensive management of long-term prescription medications should be jointly established and improved by multiple departments， and the formulation of drug catalogs should avoid including drugs with potential social harm or medication risks while complying with policy requirements. Furthermore， measures such as adding special identifiers to long-term prescriptions， providing patients with reminders about （No.YGLX202537） prescription expiration， or offering online consultations can also effectively enhance the rationality of medication use under long-term prescriptions. Currently， the implementation of long-term prescriptions in psychiatry remains challenged by inconsistencies in prescription duration， incomplete coverage of diagnostic categories， poor patient adherence， and the risk of deviation in clinical assessments. In this regard， measures such as collaborating with multiple departments to strengthen long-term prescription information management， providing matching pharmaceutical services， ensuring the quality and rationality of long-term prescription implementation， and using modern methods to screen high-risk patients can be taken to improve patient medication compliance and safety.

Objective:To summary the clinical and electrophysiological characteristics of temporal lobe epilepsy (TLE) originating from the temporal pole (TP), and to conduct brain network analysis based on stereo-electroencephalogram (SEEG) and head positron emission tomography- computed tomography (PET-CT).Methods:A retrospective analysis was conducted on patients with TLE who underwent SEEG implantation from January 1, 2019 to September 1, 2023 in Guangdong Sanjiu Brain Hospital. Based on anatomical-electrical-clinical analysis and SEEG findings, patients with seizures originating from the TP were selected. The clinical data, head magnetic resonance imaging (MRI), PET-CT, scalp electroencephalogram were reviewed, and the seizure-induced network was analyzed based on SEEG and head PET-CT.Results:A total of 108 cases of TLE were analyzed, of whom 13 cases had an epileptogenic zone located at the TP, accounting for 12% (13/108) of all TLE patients. Among them, 8 were males and 5 were females, and age of onset was (11.6±7.8) years. All of them were drug-resistant epilepsy patients, of whom 6 cases had normal cognitive function, 4 had mild cognitive abnormalities, and 3 had severe cognitive decline. A total of 59 seizures were recorded, and the occurrence rate of generalized tonic-clonic seizures (GTCS) was 42% (25/59). Seizure symptoms were classified into 3 types: the first type was hypermotor, seen in 9 patients; the second type was complex motor, seen in 2 patients; and the third type was automotor, seen in 2 patients. Head MRI showed that 9 cases had a blurring of the TP on one side, with or without hippocampal sclerosis; 2 cases had a mass at the TP without hippocampal sclerosis; 2 cases were negative on head MRI. Head PET-CT showed that 13 cases had TP hypometabolism on the lesion side, of whom 11 cases had hypometabolism involving the medial temporal lobe (mTL), posterior orbital gyrus (POG), anterior cingulate gyrus (ACG) and insular lobe at the same time, the other 2 cases combined with ipsilateral hypometabolism of the medial temporal lobe. Pathology showed that 7 cases had microcortical dysplasia of the TP; 3 had focal cortical dysplasia Ⅰ or focal cortical dysplasia Ⅱ; 2 had benign tumors. Scalp electroencephalogram showed that interictal phase was divided into 3 discharge patterns: bilateral temporal regions with prominent lesion side; bilateral anterior regions with prominent lesion side; lesion-side hemisphere with prominent temporal region. Ictal period showed 4 initial patterns: lesion-side hemispheric rhythmic spikes-slow waves or polyspikes-slow waves; lesion-side anterior region rhythmic slow waves; lesion-side anterior region low voltage fast (LVF) activities, and diffuse LVF with prominent lesion-side hemisphere. SEEG showed that 13 patients received electrode implantation with (9±2) electrodes per patient, divided into 3 seizure patterns: type 1: TP?adjacent temporal neocortex?POG, ACG and insula?mTL; type 2: TP?para hippocampal gyrus and the base of temporal lobe?ACG ,POG and insula?mTL; type 3: TP?mTL?insular lobe?POG.Conclusions:TLE originating from the TP is relatively rare, with hypermotor or complex motor as the main manifestations, and automotor being relatively less common, which is more likely to be followed by GTCS. The epileptogenic network analysis displays a tendency to spread from the TP to the frontal and insular lobes, as well as to the mTL, with the former pattern being more common. Common etiologies are cortical dysplasia and benign tumors of the TP without hippocampal sclerosis.

Objective:To explore the epileptogenic network patterns in 14 patients with mesial temporal lobe epilepsy (mTLE) originating from the amygdala.Methods:A total of 14 patients with mTLE originating from the amygdala underwent preoperative evaluation in Department of Epilepsy, Guangdong Sanjiu Brain Hospital from January 1, 2019 to December 31, 2023 were selected. A retrospective analysis was performed on the clinical data of these patients. Epileptogenic network patterns were further explored based on stereo-electroencephalogram (SEEG) and positron emission tomography-computed tomography (PET-CT).Results:Craniocerebral MRI indicated 12 patients with unilateral amygdala hypertrophy, and 2 with increased T2-FLAIR signal in the amygdala but no obvious volume change. During interictal period, scalp EEG indicated discharges in one or both temporal regions and distinguished at the lesion side. During ictal period, scalp EEG indicated that the initial side is consistent with the lesion side. Three clinical phenotypes and epileptogenic network patterns were summarized: the first type ( n=5) had clinical manifestations as aura→automotor→autonomic symptoms, with epileptic seizure starting from amygdala→hippocampus→preinsula→temporal pole (by SEEG) and low metabolism in the medial structures of the temporal lobe (by PET-CT); the second type ( n=6) had clinical manifestations as aura→hypermotor/complex motor→autonomic symptoms, with epileptic seizure starting from amygdala→hippocampus→temporal pole→frontal orbital gyrus and anterior cingulate cortex→insula (by SEEG) and low metabolism in the medial structures of the temporal lobe, temporal pole, insula, frontal-orbital gyrus, and inner frontal lobe (by PET-CT); the third type ( n=3) had clinical manifestations as aura→bilateral symmetrical dystonia→autonomic symptoms (with or without oral-alimentary automotor), with epileptic seizure starting from amygdala→hippocampus and insula→temporal pole and adjacent temporal neocortex (by SEEG) and low metabolism in the mesial structures of the temporal lobe and the insula (by PET-CT). Conclusion:The different clinical phenotypes of patients with mTLE originating from the amygdala may have equivalent epileptogenic network patterns.

Objective:To investigate the mechanism of polygonatum and astragalus compound(PA)in inhibiting the progression of lung adenocarcinoma. Methods:CCK-8 assay was used to assess the inhibitory rate of proliferation in A549 and H1299 cells treated with PA at different concentrations and to calculate the half maximal inhibitory concentration(IC50).C57BL/6 mice(KRASG12D/+;TP53flox/flox)were treated with adenovirus carrying Cre enzyme via nasal inhalation to establish a mouse model of primary lung adenocarcinoma.The model mice were fed with PA-containing diet to directly observe the effect of PA on the lung adenocarcinoma tissue.Immunohistochemical staining was used to examine the pathological status of the lung tissue.Bioinformatics analysis indicated that PA affects the progression of lung adenocarcinoma through the apelin-peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC1α)-mitochondrial brown fat uncoupling protein 1(UCP1).Real-time quantitative PCR and Western blotting analysis were used to study the effect of PA on the mRNA and protein expression levels of apelin-PGC1α-UCP1 signaling pathway related genes.An ATP detection kit and flow cytometry were used to evaluate the effect of PA on the ATP and mitochondrial ROS production,respectively,in A549 and H1299 cells.siUCP1 was used to silent the expression of UCP1 while Z160 was used to induce UCP1 overexpression in A549 and H1299 cells,and the changes in ATP and mitochondrial ROS production were examined to further investigate whether PA acts on apelin-PGC1α-UCP1 signaling pathway to affect the progression of lung adenocarcinoma. Results:PA could obviously inhibit the proliferation of A549 and H1299 cells with the IC50 values of 10.66 mg/mL for A549 cells and 9.66 mg/mL for H1299 cells.In the mouse primary lung adenocarcinoma model,PA could effectively inhibit the growth of tumor,downregulate apelin-PGC1α-UCP1 signaling pathway and inhibit the expression of lung adenocarcinoma-promoting gene UCP1.In A549 and H1299 cells,PA could significantly inhibit the expression of apelin,PGC1α and UCP1(P＜0.05),promote the production of ATP(P＜0.000 1)and ROS,restore mitochondrial oxidative phosphorylation,and inhibit aerobic glycolysis(P＜0.01).UCP1 silencing could increase the production of ATP(P＜0.01)and mitochondrial ROS and decrease the expression of key glycolysis enzymes hexokinase 2(HK2)and pyruvate kinase isozyme type M2(PKM2)(P＜0.05).Increasing the expression of UCP1 could reduce the ATP production(P＜0.01)and mitochondrial ROS generation in cells while increase the expression of HK2 and PKM2(P＜0.05).Treating cells with PA and Z160 simultaneously(PA+Z160)could reverse the inhibitory effect of PA on the ATP production and glycolysis of tumor cells(P＜0.05). Conclusion:PA can downregulate the apelin-PGC1α-UCP1 signaling pathway,inhibit mitochondrial uncoupling,restore mitochondrial oxidative phosphorylation,inhibit aerobic glycolysis,reverse the Warburg effect,and thus inhibit lung adenocarcinoma progression.

Objective:To investigate the effect of nuclear factor-erythroid 2-related factor 2 (Nrf2) gene on the proliferation and apoptosis of colorectal adenocarcinoma cells in vitro, and the role of Nrf2 gene in regulation of epithelial-mesenchymal transition (EMT) pathway.Methods:Three Nrf2 small interfering RNA (siRNA) sequences were designed and synthesized, namely siRNA-223, siRNA-538 and siRNA-756, and the unrelated sequences were designed and synthesized. The plasmids carrying various siRNA sequences of Nrf2 were constructed, and the plasmids carrying siRNA sequences and the plasmids carrying unrelated sequences were transfected into human colorectal adenocarcinoma Caco-2 cells, namely interference group and empty vector group, respectively. Additionally, Caco-2 cells without any treatment were used as the control group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting (WB) methods were used to detect the relative expression of Nrf2 gene in transcription and translation levels in each group of cells, in order to verify the interference effect of Nrf2; the siRNA with the best interference effect was selected for subsequent experiments. CCK-8 method was used to detect the proliferation ability of each group of cells (expressed as absorbance value); RT-qPCR was used to detect the relative expression of EMT pathway-related factors [vimentin (Vim), N-cadherin (N-cad) and E-cadherin (E-cad)] in transcription level in each group of cells; WB method was used to detect the expression of pro-apoptotic protein Bax in each group of cells.Results:The results of RT-qPCR and WB methods showed that compared with the control group and the empty group, the relative expression of Nrf2 gene in transcription and translation levels in Caco-2 cells of the siRNA-756 interference group were the lowest, and the differences were statistically significant (all P < 0.05). The CCK-8 results showed that the absorbance values of Caco-2 cells in the control group, empty group and siRNA-756 interference group after 48 hours of culture were (100±5)%, (94±4)% and (82±5)%, respectively; compared with the control group and the empty group, the siRNA-756 interference group had lower absorbance value, and the differences were statistically significant (all P < 0.05). The results of RT-qPCR method showed that the relative expression of Vim and N-cad in transcription level in the siRNA-756 interference group were higher than those in the control group and the empty vector group, and the differences were statistically significant (all P < 0.05); the relative expression of E-cad in transcription level was lower than those in the control group and the empty vector group, and the differences were statistically significant (both P < 0.05). The results of WB method showed that the relative expression of Bax protein in the siRNA-756 interference group was higher than that in the control group, and the difference was statistically significant ( P < 0.05). Conclusions:Interference with Nrf2 expression in vitro can weaken the proliferation and anti-apoptotic abilities of human colorectal adenocarcinoma Caco-2 cells. The mechanism may be that Nrf2 regulates the expression of Vim, N-cad and E-Cad in the EMT pathway to enhance the EMT ability of tumor cells.

Lipid metabolism disorders is a prevalent clinical symptom observed in patients with fatty liver type hepatolenticular degeneration.According to TCM,the key pathogenesis of this disease is deficiency of spleen yang.The method of warming yang and dissipating qi is the basic method to treat this disease.This article explored the pathological foundation of fatty liver type hepatolenticular degeneration based on the"spleen rules transformation".It elucidated that lipid metabolism disorder is a significant characteristic of this disease,considering both TCM and Western medicine perspectives.It also examined the treatment of fatty liver type hepatolenticular degeneration by regulating lipid metabolism through the method of warming yang and dissipating qi,with the purpose to guide the treatment of the disease.

OBJECTIVE To provide a reference for medical institutions in selecting and establishing a traditional Chinese medicine （TCM） clinical pharmaceutical care mode that suits their clinical characteristics. METHODS Combining clinical cases， this paper introduces the workflow and service content of the joint consultation mode between TCM physicians and TCM clinical pharmacists in our hospital and analyzes its effectiveness. RESULTS The workflow of the pharmaceutical care mode in our hospital involves six stages：assessing the patient’s medication status， consultation rounds and formulating medication regimen， bedside education， pharmaceutical monitoring， pharmacist rounds， and extended pharmaceutical care. The care content primarily includes thoroughly collecting clinical information and evaluating the patient’s medication regimen before the consultation. During the consultation， TCM clinical pharmacists and TCM physicians jointly developed a dosage regimen tailored to the patient’s individual conditions. After the consultation， bedside medication education was conducted to ensure the correct use of medications and a pharmaceutical monitoring plan was developed and implemented， during which the patient’s post-consultation condition changes were monitored and timely feedback to the TCM physicians for medication plan adjustments was provided， offering extended pharmaceutical care post-consultation， including medication consultation， pharmaceutical outpatient services， and joint clinics. Since its implementation， nearly 1 000 inpatients have been served annually， with a 100% medical order review rate for patients taking TCM decoction pieces. Individualized medication education reached 78.80%， and patient’s degree of satisfaction was 100%. The prescription compliance rate of TCM decoction pieces in the wards increased from 89.33% before the implementation of the joint consultation to 97.08% afterward. Additionally， the mode provided TCM-related consultations to over 1 000 patients annually and compiled and provided nearly a hundred pharmaceutical documents to healthcare personnel. CONCLUSIONS By establishing the joint consultation mode between TCM physicians and TCM clinical pharmacists and conducting TCM clinicalpharmaceutical care， the level of rational use of TCMdecoction pieces has been promoted， demonstrating the value of TCM clinical pharmacists.

ObjectiveTo provide technical support for the molecular surveillance of pathogenic bacteria strains carrying mobile colistin resistance-1 （mcr⁃1） gene isolate from inlet of wastewater treatment plants （WWTP）. MethodsThe Enterobacteriaceae strains carrying mcr⁃1 resistance gene isolate from inlet of WWTP during April 1 to June 30， 2023 in Shanghai were cultured on blood-rich and SS culture medium and were identified using a mass spectrometry analyzer. The mcr⁃1 gene and copy number were detected by real-time fluorescence quantitative PCR. Drug susceptibility test was performed by microbroth dilution method. The copy numbers of Escherichia coli carrying mcr⁃1 gene isolated from wastewater and human fecel were statistically analyzed by SPSS 25.0. ResultsA total of 14 strains carrying the mcr⁃1 gene were isolated from 49 WWTP samples， and the positive isolation rate was 28.6%， including 12 non-diarrheal E. coli strains and 2 Klebsiella pneumoniae strains. The drug susceptibility results showed that all 14 strains were multi-drug resistant bacteria. They were all sensitive to imipenem and tigecycline， but were ampicillin- and cefazolin-resistant. There was no significant difference in the copy number between human-sourced diarrheal E. coli and wastewater-sourced non-diarrheal E. coli （t=0.647， P>0.05）. ConclusionThe isolation and identification of strains carrying the mcr⁃1 gene from inlet of WWTP samples were firstly established in Shanghai. The multi-drug resistance among the isolated strains is severe. To effectively prevent and control the spread of colistin-resistant bacteria， more attention should be paid to the surveillance of mcr⁃1 gene.