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.

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 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.

Objective:To study the position of computed tomography(CT)slice of marker points of radiotherapy,which was determined by control scan(CS)method,on the application effect of patients with head and neck tumors who received radiotherapy.Methods:Based on Control Scan(CS)method,a calculator program of mark-point slice position was made,which was an enterprise WeChat program that could be used in calculating position and CT position scan of patients with head and neck tumor(slice thickness was 3mm).A total of 60 patients with head and neck tumor were selected,and the patients who underwent CT positioning scan by using CS method were divided into observation group,and patients who underwent CT position scan by using conventional method were divided into control group,with 30 cases in each group.The number of cases with three metal marker points displayed at the same slice,and the number of slices containing the CT images of marker point between the located CT scan were compared.Results:The number of patients in the observation group and the control group who showed three markers at the same level at the same time were respectively 26 cases and 13 cases,and observation group increased by 13 cases(43.4%)than control group,and the difference was significant(x2=12.382,P<0.05).The number of CT images with only 1 slice of observation group and control group were respectively 4 cases and 0 cases,which increased by 4 cases(13.3%)than the control group,and the difference was significant(x2=2.411,P<0.05).Conclusions:The CT localization scan of radiotherapy,which uses CS to assist patients with head and neck tumor,can precisely calculate and obtain the primary position of target of CT localization scan.It can take the images of 3 mental marker points of patient who receives radiotherapy to occur at the same CT slice as soon as possible,which has better application effect.It can effectively improve the convenience and work effectiveness of radiotherapy.

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.

Objective To evaluate early outcomes of transthoracic pulmonary valve implantation for the treatment of moderate and severe pulmonary regurgitation by using homemade self-expanding valve (SalusTM). Methods Patients with severe pulmonary regurgitation who underwent transthoracic pulmonary valve implantation in Guangdong Provincial People’s Hospital from September 2, 2021 to November 25, 2022 were prospectively enrolled. The early postoperative complications and improvement of valve and heart function were summarized and analyzed. Results A total of 25 patients were enrolled, including 16 males and 9 females, with an average age of 24.5±1.5 years and an average weight of 57.0±3.0 kg. The mean systolic diameters of the bifurcation near the main pulmonary artery, the stenosis of the middle segment of the aorta and near the valve of the right ventricular outflow tract of the patients were 31.8±7.4 mm, 30.6±5.9 mm and 38.4±8.0 mm, respectively. All patients were successfully implanted with valves, and there were no serious complications such as death, coronary compression, stent fracture, valve displacement and infective endocarditis in the early postoperative period. The indexed left atrial longitudinal diameter, indexed right atrial longitudinal diameter, and indexed right ventricular outflow tract anteroposterior diameter decreased significantly after the operation. The degree of tricuspid and pulmonary valve regurgitation and the indexed regurgitation area decreased significantly. The above differences were statistically significant (P<0.05). Conclusion The early outcomes of transthoracic pulmonary valve implantation with homemade self-expanding pulmonary valve (SalusTM) in the treatment of severe pulmonary regurgitation is relatively good, and the long-term outcomes need to be verified by the long-term follow-up studies with large samples.

Objective:To understand the infection status, epidemiological characteristics and drug resistance of Diarrheagenic Escherichia coli (DEC) in Shanghai and provide evidence for the disease surveillance. Methods:The epidemiological data of diarrhea cases in Shanghai from 2016 to 2022 were collected from Shanghai Diarrhea Comprehensive Surveillance System, and stool samples were collected from the cases for DEC detection. The drug resistance data was obtained from Chinese Pathogen Identification Network. Statistical analysis was conducted by using χ2 and fisher test. Results:In 24 883 diarrhea cases detected during 2016-2022, the DEC positive rate was 9.13% (2 271/24 883), the single DEC positive rate was 8.83% (2 197/24 883) and the mixed DEC positive rate was 0.30% (74/24 883). The main type of DEC was Enterotoxigenic Escherichia coli (ETEC) [4.33% (1 077/24 883)]. The DEC positive rate was highest in people aged ≤5 years 18.48% (22/119). The annual peak of DEC positive rate was observed during July - September [5.91% (1 470/24 883)]. The DEC positive rate were 9.47% (554/5 847) and 9.02% (1 717/19 036) in urban area and in suburbs, respectively, Enteroaggregative Escherichia coli (EAEC) [3.98% (233/5 847)] and ETEC [4.56% (868/19 036)] were mainly detected. From 2016 to 2019, the DEC positive rate was 9.42% (1 821/19 330), while it was 8.10% (450/5 553) from 2020 to 2022, the main DEC types were ETEC (4.87%, 941/19 330) and EAEC (4.70%, 261/5 553). The multi-drug resistance rate was 40.21% (618/1 537). The top three antibiotics with high drug resistance rates were ampicillin [64.74% (995/1 537)], nalidixic acid [58.49% (899/1 537)] and tetracycline [45.09% (693/1 537)]. Conclusions:Compared with 2016- 2019, a decrease in DEC detection rate was observed during 2020-2022, and the main type of DEC detected shifted from ETEC to EAEC. The prevalence of multi-drug resistance was severe. Therefore, it is necessary to further strengthen the surveillance for DEC drug resistance and standardize the use of clinical antibiotics.

Objective To analyze and summarize the early and medium-term outcomes of self-expanding interventional pulmonary valve stent (SalusTM) for right ventricular outflow tract dysfunction with severe pulmonary valve regurgitation. Methods We established strict enrollment and follow-up criteria. Patients who received interventional pulmonary valve in transthoracic implantation in Guangdong Provincial People’s Hospital from September 2, 2021 to July 18, 2023 were prospectively included, and all clinical data of patients were collected and analyzed. Results A total of 38 patients with severe pulmonary regurgitation were included, with 23 (60.5%) males and 15 (39.5%) females. The mean age was 24.08±8.12 years, and the mean weight was 57.66±13.54 kg. The preoperative mean right ventricular end-diastolic volume index (RVEDVI) and right ventricular end-systolic volume index (RVESVI) were 151.83±42.84 mL/m2 and 83.34±33.05 mL/m2, respectively. All patients successfully underwent transcatheter self-expandable pulmonary valve implantation, with 3 (7.9%) patients experiencing valve stent displacement during the procedure. Perioperative complications included 1 (2.6%) patient of postoperative inferior wall myocardial infarction and 1 (2.6%) patient of poor wound healing. The median follow-up time was 12.00 (6.00, 17.50) months. During the follow-up period, there were no deaths or reinterventions, and no patients had recurrent severe pulmonary regurgitation. Three (7.9%) patients experienced chest tightness and chest pain, and 1 (2.6%) patient developed frequent ventricular premature beats. Compared with preoperative values, the right atrial diameter, right ventricular diameter, and tricuspid annular plane systolic excursion were significantly reduced at 6 months and 1 year postoperatively, with improvement in the degree of pulmonary regurgitation (P<0.01). Compared with preoperative values, RVEDVI and RVESVI decreased to 109.51±17.13 mL/m2 and 55.88±15.66 mL/m2, respectively, at 1 year postoperatively (P<0.01). Conclusion 　Self-expanding interventional pulmonary valve in transthoracic implantation is safe and effective for severe pulmonary valve regurgitation and shows good clinical and hemodynamic results in one-year outcome.

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 evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older. METHODS: In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m² and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m² or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders. RESULTS: During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD. CONCLUSIONS The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.