Alzheimer's disease （AD）， a degenerative disease of the central nervous system， is characterized by progressive degradation of learning， memory， and cognitive functions. Currently， few drugs are available for treating AD， and their effects are limited. Berberine （BBR） is a natural isoquinoline （quaternary ammonium-like） with a wide range of pharmacological effects. Studies have proven that BBR has good potential in the treatment of AD. Specifically， BBR can inhibit the generation， aggregation， and neurotoxicity of amyloid-β and the hyperphosphorylation of Tau protein， promote the clearance of phosphorylated Tau protein， reduce the cholinesterase activity， neuroinflammation， and oxidative stress， regulate neuronal apoptosis， improve the mitochondrial function and glucose and lipid metabolism， suppress the monoamine oxidase activity， and modulate gut microbiota. In addition， researchers have ameliorated the low bioavailability of BBR. Probing into the potential targets is hoped to provide a reference for further research on the prevention and treatment of AD by BBR.

Objective To identify the core constitutions and prodromal symptoms of relapse in schizophrenia patients using network analysis,and to analyze their relationships as well as gender differences.Methods Schizophrenia patients hospitalized in the psychiatry department of Hunan Brain Hospital in Hunan Province between October 2022 and December 2023 were selected as survey participants.A general information questionnaire,a Traditional Chinese Medicine Constitution Scale,and a Schizophrenia Prodromal Symptoms of Relapse Scale were used for investigation.Network anal-ysis was conducted using R language.Results The core constitutions of schizophrenia patients were qi deficiency constitution[Expected Influence(EI)=1.08]and dampness-heat constitution(EI=1.00),and the core prodromal symptoms of relapse were depression/withdrawal(EI=0.84)and ini-tial psychotic manifestations(EI=0.81).There were statistically significant differences in constitutions of traditional Chinese medicine and prodromal symptoms of relapse between patients of different genders(P＜0.05).Females mainly exhibited qi deficiency constitution(EI=1.20)with anxiety as the core prodromal symptom(EI=0.98),while males mainly exhibited yin deficiency constitution(EI=1.05)with depression/withdrawal as the core prodromal symptom(EI=1.00).Conclusion Healthcare professionals can early identify core prodromal symptoms of relapse by core imbalanced constitutions of schizophrenia patients,and develop precise intervention strategies,thereby promoting changes in their network structure,preventing disease relapse,and improving patients'quality of life.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Immunotherapy has become a pivotal modality in clinical cancer treatment. However, its effectiveness is limited to a small subset of patients due to the low antigenicity, impaired innate response, and various adaptive immune resistance mechanisms of the tumor microenvironment (TME). Accumulating evidence reveals the critical roles of metal elements in shaping immunity against tumor progression and metastasis. The marriage of metalloimmunotherapy and nanotechnology further presents new opportunities to optimize the physicochemical and pharmacokinetic properties of metal ions in a precise spatiotemporal control manner. Several metallodrugs have demonstrated encouraging immunotherapeutic potential in preliminary studies and are currently undergoing clinical trials at different stages, yet challenges persist in scaling up production and addressing long-term biosafety concerns. This review delineates how metal materials modulate biological activities across diverse cell types to orchestrate antitumor immunity. Moreover, it summarizes recent progress in smart drug delivery-release systems integrating metal elements, either as cargo or vehicles, to enhance antitumor immune responses. Finally, the review introduces current clinical applications of nanomedicines in metalloimmunotherapy and discusses potential challenges that impede its widespread translation into clinical practice.

OBJECTIVES: We present a new low-dose CT reconstruction method using sub-pixel and anisotropic diffusion. METHODS: The sub-pixel intensity values and their second-order differences were obtained using linear interpolation techniques, and the new gradient information was then embedded into an anisotropic diffusion process, which was introduced into a penalty-weighted least squares model to reduce the noise in low-dose CT projection data. The high-quality CT image was finally reconstructed using the classical filtered back-projection (FBP) algorithm from the estimated data. RESULTS: In the Shepp-Logan phantom experiments, the structural similarity (SSIM) index of the CT image reconstructed by the proposed algorithm, as compared with FBP, PWLS-Gibbs and PWLS-TV algorithms, was increased by 28.13%, 5.49%, and 0.91%, the feature similarity (FSIM) index was increased by 21.08%, 1.78%, and 1.36%, and the root mean square error (RMSE) was reduced by 69.59%, 18.96%, and 3.90%, respectively. In the digital XCAT phantom experiments, the SSIM index of the CT image reconstructed by the proposed algorithm, as compared with FBP, PWLS-Gibbs and PWLS-TV algorithms, was increased by 14.24%, 1.43% and 7.89%, the FSIM index was increased by 9.61%, 1.78% and 5.66%, and the RMSE was reduced by 26.88%, 9.41% and 18.39%, respectively. In clinical experiments, the SSIM index of the image reconstructed using the proposed algorithm was increased by 19.24%, 15.63% and 3.68%, the FSIM index was increased by 4.30%, 2.92% and 0.43%, and the RMSE was reduced by 44.60%, 36.84% and 15.22% in comparison with FBP, PWLS-Gibbs and PWLS-TV algorithms, respectively. CONCLUSIONS The proposed method can effectively reduce the noises and artifacts while maintaining the structural details in low-dose CT images.
Tomography, X-Ray Computed/methods* ; Algorithms ; Phantoms, Imaging ; Anisotropy ; Image Processing, Computer-Assisted/methods* ; Humans ; Radiation Dosage

OBJECTIVES: To investigate the regulatory role of astrocytes in the dorsomedial hypothalamus (DMH) during sevoflurane anesthesia emergence. METHODS: Forty-two male C57BL/6 mice were randomized into 6 groups (n=7) for assessing astrocyte activation in the dorsomedial hypothalamus (DMH) under sevoflurane anesthesia. Two groups of mice received microinjection of agfaABC1D promoter-driven AAV2 vector into the DMH for GCaMP6 overexpression, and the changes in astrocyte activity during sevoflurane or air inhalation were recorded using calcium imaging. For assessing optogenetic activation of astrocytes, another two groups of mice received microinjection of an optogenetic virus or a control vector into the DMH with optic fiber implantation, and sevoflurane anesthesia emergence was compared using behavioral experiments. In the remaining two groups, electroencephalogram (EEG) recording during sevoflurane anesthesia emergence was conducted after injection of the hChR2-expressing and control vectors. Anesthesia induction and recovery were assessed by observing the righting reflex. EEG data were recorded under 2.0% sevoflurane to calculate the burst suppression ratio (BSR) and under 1.5% sevoflurane for power spectrum analysis. Immunofluorescence staining was performed to visualize the colocalization of GFAP-positive astrocytes with viral protein signals. RESULTS: Astrocyte activity in the DMH decreased progressively as sevoflurane concentration increased. During 2.0% sevoflurane anesthesia, the mice injected with the ChR2-expressing virus exhibited a significantly shortened wake-up time (P<0.05), and optogenetic activation of the DMH astrocytes led to a marked reduction in BSR (P<0.001). Under 1.5% sevoflurane anesthesia, optogenetic activation resulted in a significant increase in EEG gamma power and a significant decrease in delta power in ChR2 group (P<0.01). CONCLUSIONS Optogenetic activation of DMH astrocytes facilitates sevoflurane anesthesia emergence but does not significantly influence anesthesia induction. These findings offer new insights into the mechanisms underlying anesthesia emergence and may provide a potential target for accelerating postoperative recovery and managing anesthesia-related complications.
Animals ; Astrocytes/physiology* ; Sevoflurane ; Mice, Inbred C57BL ; Mice ; Male ; Electroencephalography ; Anesthetics, Inhalation/pharmacology* ; Hypothalamus/cytology* ; Anesthesia Recovery Period ; Methyl Ethers/pharmacology*

Objective To explore the active monitoring strategies for hypoglycemia in hospitalized dia-betic patients,as well as their clinical symptom characteristics and influencing factors.Methods A retrospec-tive search was conducted on all inpatients in a tertiary hospital in 2023.The hospital's electronic medical re-cord system was manually retrieved through the inpatient numbers of the patients.Adult inpatients with dia-betes who experienced hypoglycemia were included as the research subjects,and the general conditions and possible hypoglycemia-related risk factors were collected.Embed the hypoglycemic electronic trigger program in China Hospital Pharmacovigilance System(CHPS),reviewed the original medical records of patients with positive trigger triggering,and calculated the positive predictive value(PPV).Searched for the number of hy-poglycemic adverse reaction cases voluntarily reported by this hospital during the same period from National Adverse Reaction Monitoring System and compared with the actual number of hypoglycemic cases discovered.Patients with suspected drug-induced hypoglycemia were divided into the symptomatic group and the asymp-tomatic group based on whether they presented hypoglycemia-related symptoms.Multivariate logistic regres-sion analysis was applied to analyze the influencing factors.Results A total of 1 001 adult hospitalized diabet-ic patients with hypoglycemia were included in the study.Among them,725 cases were suspected of drug-in-duced hypoglycemia,and 495 cases were suspected of hypoglycemia caused by drug interactions.After manual review,131 cases of drug-induced hypoglycemia patients had clinical symptoms,and hypoglycemic adverse re-action events should be reported,PPV of this trigger for symptomatic hypoglycemia was 18.1%(131/725).However,the number of hypoglycemic adverse reactions spontaneously reported through National Adverse Reaction Monitoring System by this hospital during the same period was 4 cases,and the reporting rate was only 3.1%(4/131).Multivariate logistic regression analysis showed that aging and grade 2 hypoglycemia were risk factors for the occurrence of related symptoms in patients with suspected drug-induced hypoglycemia(P<0.05),while surgery,type 2 glucosuria,unclassified diabetes,and the use of insulin secretagogues were protective factors(P<0.05).Conclusion Drug-induced hypoglycemia dominates among hospitalized diabetic patients,and age,hypoglycemia grade,inpatient department using insulin secretagogues,diabetes diagnosis and classification are closely related to the occurrence of clinical hypoglycemia-related symptoms.Active monito-ring through CHPS can effectively increase the detection rate and reporting rate of hypoglycemic adverse e-vents in hospitalized diabetic patients.

Background Atherosclerotic cardiovascular disease (ASCVD) is a major contributor to the global burden of cardiovascular diseases. However, evidence from meta-analyses on the association between ambient ozone exposure and ASCVD risk remains relatively insufficient. Objective To explore the epidemiological association between ambient ozone exposure and ASCVD, providing scientific evidence for ASCVD prevention and control from the perspective of environmental risk factor management. Methods We systematically searched PubMed, Web of Science, Embase, the Cochrane Library, CNKI, Wanfang Database, CBM, and VIP for published epidemiological studies on the relationship between ambient ozone exposure and ASCVD from January 2007 to December 2023. We performed quality assessment and data extraction of the included studies, and utilized meta-analysis to evaluate the effects of short-term and long-term ozone exposure on different ASCVD outcomes, including mortality and incidence of ischemic heart disease (IHD) and ischemic stroke (IS). Results A total of 24 studies were included based on a set of predetermined eligibility criteria. The meta-analysis results indicated that short-term ozone exposure was associated with an increased risk of ASCVD mortality and incidence. Specifically, short-term ozone exposure was significantly associated with an elevated risk of IHD mortality (combined RR=1.011, 95%CI: 1.008, 1.015; P < 0.05). Additionally, short-term ozone exposure was significantly linked to increased IS mortality (combined RR=1.005, 95%CI: 1.003, 1.008; P < 0.05) and incidence (combined RR=1.015, 95%CI: 1.003, 1.027; P < 0.05). Conclusion Short-term exposure to ambient ozone significantly elevates acute cardiovascular disease risk. However, the epidemiological association between long-term ozone exposure and ASCVD remains inconclusive. Future high-quality cohort studies with refined exposure assessment methods are warranted to elucidate the chronic cardiovascular effects of ozone exposure.

To investigate the role of intestinal fungi in the progression of heart failure (HF) associated with chronic kidney disease (CKD).

OBJECTIVE: To explore the efficacy differences among different acupuncture frequencies for pain of temporomandibular disorders (TMD). METHODS: A total of 42 patients with TMD pain were randomly divided into a low-frequency group, a medium-frequency group, and a high-frequency group, with 14 patients in each group. All groups received acupuncture treatment at bilateral Hegu (LI4) and Yanglingquan (GB34), as well as ipsilateral Tinggong (SI19), Jiache (ST6), and Xiaguan (ST7), with each session lasting 30 minutes. The low-frequency group received acupuncture once per week, the medium-frequency group received acupuncture twice per week, and the high-frequency group received acupuncture three times per week, for a total duration of four weeks. The graded chronic pain scale (GCPS) score, visual analogue scale (VAS) score, jaw functional limitation scale-20 (JFLS-20) score, and pressure pain threshold (PPT) were assessed in the three groups before and after treatment, as well as at the four-week follow-up after treatment completion. RESULTS: Compared before treatment, GCPS and JFLS-20 scores were significantly decreased in all the groups after treatment (P<0.05), and VAS scores were significantly decreased in the high-frequency and medium-frequency groups (P<0.05), PPT values at different measurement sites were increased significantly in the high-frequency group (P<0.05). After treatment, GCPS, JFLS-20, and VAS scores in the high-frequency group were lower than those in the medium-frequency and low-frequency groups (P<0.05), while some PPT values were higher than the other two groups (P<0.05). At follow-up, GCPS, JFLS-20, and VAS scores remained significantly lower in all the groups compared to baseline (P<0.05), PPT values were increased significantly in the high-frequency and medium-frequency groups (P<0.05), with the high-frequency group showing lower GCPS, JFLS-20, and VAS scores and higher PPT values compared to the other two groups (P<0.05). CONCLUSION Acupuncture three times per week is more effective in reducing TMD pain intensity compared to once or twice per week, and can also alleviate some mandibular functional impairments. The therapeutic effects persist for at least four weeks after treatment completion.
Humans ; Male ; Female ; Adult ; Acupuncture Therapy/methods* ; Temporomandibular Joint Disorders/physiopathology* ; Middle Aged ; Young Adult ; Treatment Outcome ; Acupuncture Points ; Pain Management ; Adolescent ; Pain Measurement